RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids

RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids Beverly A. Teicher, Thomas S. Dexheimer, Thomas Silvers, Nathan P. Coussens, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6602839/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Sep, 2025 Read the published version in Cancer Chemotherapy and Pharmacology → Version 1 posted 7 You are reading this latest preprint version Abstract The alternative splicing of mRNA precursors allows one gene to yield multiple proteins with distinct functions. CDC-like kinases (CLKs) serve as pivotal regulators of alternative splicing. Control of protein expression also occurs at the level of DNA through histone methylation and demethylation. We investigated the activity of two CLK inhibitors, cirtuvivint and CC-671, and the LSD1 inhibitor iadademstat alone and in combination with anticancer drugs or investigational agents. Well-characterized patient-derived cancer cell lines from the PDMR ( https://pdmr.cancer.gov/models/database.htm ) were used along with standard human cancer cell lines. Multi-cell type (mct) tumor spheroids were grown from a ratio of 6:2.5:1.5 malignant cells, endothelial cells, and mesenchymal stem cells. Following three days of growth, the spheroids were exposed to the single agents or combinations at concentrations up to the clinical C max value for each agent, if known. After seven days of exposure, cell viability was assessed using the CellTiter-Glo 3D assay and spheroid volume was assessed by bright field imaging. Several of the targeted oncology drugs exhibited additive and greater-than-additive cytotoxicity when combined with a CLK inhibitor, or the LSD1 inhibitor. These agents included the XPO1 inhibitor, eltanexor, and the KRAS G12D specific inhibitor MRTX-1133 which had activity in tumor lines harboring the KRAS G12D mutation. LSD1 inhibition was effective with ubiquitin proteasome pathway inhibitors. The full data sets are available on PubChem. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION The spliceosome, a critical intracellular organelle, is multi-megadalton complex composed of over 100 proteins including 5 small nuclear ribonucleoproteins. Cancer cells often have cancer type-specific RNA splicing alterations. Most multi-exon human genes undergo alternative splicing, allowing multiple mature mRNAs to be derived from a single gene [ 1 , 2 ]. Thus, 25,000 genes can code for well over 100,000 proteins. Pre-mRNA splicing, the process of removing introns from precursor messenger RNA, is critical in the post-transcriptional regulation of gene expression [ 3 ]. Serine/arginine (SR) family proteins control the patterns of alternative splicing in pre-mRNA and enhance splicing from nearby splice sites by interacting with exonic and intronic splicing enhancer sequences in pre-mRNA [ 3 ]. SR-proteins require phosphorylation by SR protein kinases (SRPKs), protein kinase B (PKB/AKT), NIMA-related kinase2 (NEK2), PRP4 kinase (PRP4K) dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), cAMP-dependent protein kinase (PKA) or by the CDC-like kinases (CLKs) to be active [ 4 ]. The CLKs regulate transcript RNA splicing through SR protein phosphorylation [ 5 ]. Cirtuvivint is a pan CDC-like kinase (CLK1-4) and dual specificity tyrosine kinase (DYRK1-4) inhibitor which targets mRNA splicing and the Wnt pathway which is in clinical trial [ 6 ]. Cirtuvivint exposure disrupts spliceosome activity and decreases production of Wnt signal pathway splicing variants. A Phase I clinical trial of cirtuvivint by oral administration, assessing dose escalation is currently active but not recruiting (NCT03355066) and the combination of cirtuvivint with ASTX727 in patients with acute myeloid leukemia or myelodysplastic syndromes is actively accruing patients (NCT06484062) [ 5 ]. CC-671, a CLK/TTK inhibitor has an inhibitory repertoire similar to cirtuvivint. TTK, also called Monopolar spindle 1 (Mps1), is a dual serine/threonine kinase that regulates the spindle assembly checkpoint, controlling cellular progression through mitosis [ 7 , 8 ]. CC-671 had in vivo activity in human tumor xenografts due to dual inhibition of CLK2/TTK [ 4 ]. Lysine-specific demethylase 1α (LSD1) encoded by the KDM1A gene, is a lysine demethylase which has recurrent mutations, translocations, and somatic copy number gains or losses in human tumors [ 9 , 10 ]. LSD1/KDM1A removes mono- and dimethyl groups of histone H3 lysine-4 (H3K4), lysine-9 (H3K9) as well as non-histone substrates [ 11 , 12 ]. LSD1 interacts with other chromatin regulators including histone deacetylases (HDAC)-1, 2 and 3, and DNA methyltransferase 1 (DNMT1). LSD1 is a component of a multi-subunit complex causing transcription activation or repression [ 13 ]. LSD1 non-histone substrates are associated with the regulation of cell cycle progression and apoptosis. LSD1/KDM1A expression is associated with poor prognosis in prostate, breast, lung, bladder, colorectal cancer and neuroblastoma. Iadademstat is a potent LSD1 inhibitor with an IC 50 of 18 nM and > 1000-fold higher selectivity towards LSD1 compared to related FAD-dependent aminoxidases [ 14 , 15 ]. In AML models, LSD1 inhibition did not alter genome methylation but did increase me 2 H3K4 at LSD1 target genes [ 16 – 18 ]. In a small cell lung cancer xenograft, treatment with iadademstat resulted in NOTCH activation and ASCL1 suppression decreasing neuroendocrine properties [ 19 ]. With the complexity of cancer genomic alterations, single targeted drugs are usually not sufficient to impact malignant disease, and combinations of targeted drugs are necessary for effective treatment. The current study was undertaken to explore the activity of RNA processing and epigenetic inhibitors in combination with other targeted agents and standard-of-care drugs in a mct-spheroid model from patient-derived tumor cell lines of the PDMR ( https://pdmr.cancer.gov/ ) or standard tumor cell lines and stromal cells. The full data sets are available at the PubChem files listed on Table 4 . MATERIALS AND METHODS C ompounds . The drugs and investigational agents: cirtuvivint (SM08502; NSC835563), CC-671 (NSC850746), iadademstat (NSC806812), vemurafenib (NSC761431), tapotoclax (NSC804041), sotorasib (NSC818433), adagrasib (NSC831453), MRTX-1133 (NSC836407), BAY2416964 (NSC825713), copanlisib (NSC816437), inavolisib (NSC800729), abemaciclib (NSC768073), osimertinib (NSC779217), entinostat (NSC756642), eltanexor (KPT-8602, NSC794443), venetoclax (NSC766270), ceralasertib (NSC777638), bortezomib (NSC756655), olaparib (NSC753686), talazoparib (NSC767125), adavosertib (NSC754677), alisertib (NSC759677), ART-558 (NSC835418), aza-T-dCyd (NSC777586), AZD-1390 (NSC803789), belinostat (NSC758774), camonsertib (NSC841442), CPI-455 (NSC825282), decitabine (NSC127716), elimusertib (NSC800525), ixazomib (NSC758254), KSQ-4279 (NSC840948), panobinostat (NSC761190), peposertib (NSC802822), pevonedistat (NSC761192), R306465 (NSC773264), selinexor (NSC780203), TAK-243 (NSC785004), tazemetostat (NSC777109), topotecan (NSC609699), TP-3654 (NSC805149), eribulin (NSC707389), etoposide (NSC141540), carboplatin (NSC241240), cisplatin (NSC119875), gemcitabine (NSC613327), 5-fluorouracil (NSC19893), SN-38 (NSC673596), oxaliplatin (NSC266046), paclitaxel (NSC125973), and doxorubicin (NSC123127), were obtained from the National Cancer Institute (NCI) Developmental Therapeutics Program Chemical Repository [ 20 ]. The FDA-approved anticancer drug set is available from the Developmental Therapeutics Program at https://dtp.cancer.gov/organization/dscb/obtaining/available plates.htm. The drugs and investigational agents used were demonstrated to be >95% pure by proton nuclear magnetic resonance and liquid chromatography/mass spectrometry. The stock solutions were prepared in dimethyl sulfoxide (DMSO, Sigma-Aldrich, St. Louis, MO, cat. D2650), except for the platinum complexes which were prepared in saline (Quality Biological, Gaithersburg, MD, cat. 114-055-101), at 800-fold the tested concentration and stored at -70°C prior to their use. All drugs and investigational agents were tested over a range starting from a high concentration at or near the clinical C max and decreasing in half-log increments. If the clinical C max for an agent had not been determined, the highest concentration tested was 10 µM ( Table 1 ). Cell Lines . The patient-derived cancer (PDC) cell lines include 16 colon adenocarcinoma lines: 186277-243-T-J2-PDC, 188146-221-R-J1-PDC, 282377-053-R-J1-PDC, 381356-305-R-J1-PDC, 435261-313-R-J1-PDC, 439559-082-T-J2-PDC, 519858-162-T-J1-PDC, 616215-338-R-J1-PDC, 695427-040-R-J1-PDC, 233499-124-R-J2-PDC, 817829-284-R-J1-PDC, 825966-067-R-J1-PDC, 857933-349-R-J2-PDC, 996289-038-R-J1-PDC, 997537-175-T-J1-PDC, and 947758-054-R-J2-PDC; 16 pancreatic carcinoma lines: 217524-143-R1-J4-PDC, 227483-062-R1-J1-PDC, 242566-281-R-J2-PDC, 292921-168-R-J2-PDC, 323965-272-R-J2-PDC, 377384-186-R-J1-PDC, 422866-222-R5-J1-PDC, 454973-116-R2-J3-PDC, 485176-168-R4-J1-PDC, 485368-065-R4-J2-PDC, 521955-158-R2-J5-PDC, 777334-354-R1-J3-PDC, 885724-159-R-J1-PDC, 966289-007-R4-J1-PDC, K24384-001-R-PDC, and 496974-208-R-J2-PDC; 6 bladder carcinoma lines: 168753-222-R-J1-PDC, 324938-238-R-J1-PDC, 565232-114-T-J1-PDC, 648629-189-R-J1-PDC, 883617-216-R-PDC, and 855422-203-R-J1-PDC; 7 endometrial carcinomas: 379773-124-R-J2-PDC, 598228-144-R-J1-PDC, 633275-114-R-J1-PDC, 636577-100-R-J1-PDC, 922993-354-T-J2-PDC, and 876862-298-R-J1-PDC; 3 head & neck squamous carcinoma: 328373-195-R-J1-PDC, 628569-122-R-J1-PDC, and 874868-142-R-J2-PDC; 4 melanoma: 156681-154-R-J1-PDC, 276233-004-R-J1-PDC, 299254-011-R-J1-PDC, and 876135-273-R-J2-PDC; 3 NSCLC: 349418-098-R-PDC, 653999-131-R-J2-PDC, and LG0703-F948-PDC; 2 breast carcinoma: 171881-019-R-J1-PDC and 885512-296-R-J2-PDC; 2 MPNST: 317291-083-R-J1-PDC and 596521-263-R-J1-PDC; 1 ovarian carcinoma: 556581-035-R-J1-PDC; 1 renal cell carcinoma: 743489-274-T-PDC; and 1 Merkel cell tumor: 138582-337-R-J1-PDC, were obtained from the NCI Patient-Derived Models Repository (PDMR, https://pdmr.cancer.gov/) ( Table 2 ). In addition, several standard human tumor cell lines were used including: 786-0 and A498 renal cell carcinoma, IGROV1, NCI/ADR-RES and OVCAR-5 ovarian carcinoma; MDA-MB-231, MDA-MB-468, and SUM149PT TNBC; NCI-H1876, NCI-H196, NCI-H211 and SW 1271 SCLC; A375 melanoma and K562 leukemia were obtained from the NCI Tumor Repository ( Table 2 ). Pooled donor human umbilical vein endothelial cells (HUVEC, Lonza, cat. CC-2519) and human mesenchymal stem cells (hMSC, Lonza, cat. PT-2501) were purchased from Lonza (Walkersville, MD). Cell Culture . All cells were maintained in an incubator at 37°C and 5% CO 2 with 95% humidity. The PDC lines were cultured according to standard operating procedures established by the NCI PDMR (https://pdmr.cancer.gov). Briefly, all PDCs were thawed and cultured in Matrigel-coated flasks prepared with a working solution of 1X Ham's F-12 nutrient mix, without supplementation (Invitrogen, Waltham, MA, cat. 11765054), 100 U/mL penicillin-streptomycin (Invitrogen, cat. 15140122), and 2.5% Matrigel (Corning Inc., Corning, NY, cat. 354248) for the first three passages. All PDCs were cultured in complete DMEM/F-12 media containing advanced DMEM/F-12 (Invitrogen, cat. 12634028), 4.9% defined fetal bovine serum, heat inactivated (HyClone Laboratories Inc., Logan, UT, cat. SH30070.03HI), 389 ng/mL hydrocortisone (Sigma-Aldrich, cat. H4001), 9.7 ng/mL human EGF recombinant protein (Invitrogen, cat. PHG0313), 23.4 µg/mL adenine (Sigma-Aldrich, cat. A2786), 97.3 U/mL penicillin-streptomycin (Invitrogen, cat. 15140122), 1.9 mM L-glutamine (Invitrogen, cat. 25030081), and 9.7 µM Y-27632 dihydrochloride (Tocris Bioscience, Bristol, United Kingdom, cat. 1254). The PDCs were cultured in complete DMEM/F12 media without 10 µM Y-27632 dihydrochloride for at least two passages prior to the screen, unless specified otherwise ( Table 3 ). The established cell lines were cultured in RPMI-1640 medium, HEPES (Invitrogen, cat. 22400105) with 10% defined fetal bovine serum (HyClone Laboratories Inc., cat. SH30070.03) and 2 mM L-glutamine (Invitrogen, cat. 25030081), unless specified otherwise ( Table 3 ). The pooled donor HUVEC and hMSC were cultured in endothelial cell growth medium 2 (PromoCell, Heidelberg, Germany, cat. C-22011) and mesenchymal stem cell growth medium 2 (PromoCell, cat. C-28009). For all experiments, HUVEC and hMSCs were used at passages ≤5, while the malignant cell lines were used at passages ≤15. Samples of the cell lines were collected at regular intervals throughout the screening process for short tandem repeat (STR) profiling and mycoplasma testing by Labcorp (Laboratory Corporation of America Holdings, Burlington, NC, formerly known as Genetica DNA Laboratories) to confirm their authenticity and integrity. High-throughput Drug Combination Screening. Prior to their inoculation into microplates, malignant cells, HUVEC, and hMSC were removed from T flasks using TrypLE express (Invitrogen, cat. 12605036) and harvested by centrifugation for 5 min at 233 × g. Following removal of the supernatant, the cells were resuspended in fresh medium and counted using a Cellometer auto T4 bright field cell counter (Nexcelom, Lawrence, MA) and trypan blue to distinguish viable cells. Multi-cell type (mct) tumor spheroids were grown from the mixture of three cell types: 60% malignant cells, 25% HUVECs, and 15% hMSCs as described previously 2]. Mixed cell suspensions of 50 µL were dispensed into the wells of 384-well black/clear round-bottom ULA spheroid microplates (Corning Inc., cat. 3830). Following inoculation, the microplates were transferred to an incubator (Thermo Fisher Scientific, Waltham, MA) and maintained at 37 °C and 5% CO 2 with 95% humidity. Three days after inoculation, test agents or controls were delivered to the wells of microplates. The approved and investigational anticancer agents, prepared as 800× stock solutions, were subsequently transferred in 62.5 nL volumes to the appropriate wells of microplates using an I.DOT non-contact dispenser (DISPENDIX, Stuttgart, Germany) to achieve a 1x final concentration. All anticancer agents and their combinations were tested in quadruplicate. Additionally, each microplate included a DMSO vehicle control ( n = 16) and a cytotoxicity control (1 µM staurosporine and 3 µM gemcitabine, n = 20). After delivery of the test agents and controls, the microplates were returned to the incubator for 7 days. Ten days after inoculation, the assay was completed with the addition of 20 µL CellTiter-Glo 3D (Promega, Madison, WI, cat. G9683) to each well. Next, the microplates were placed on a microplate shaker for 5 min. After 25 min of incubation at room temperature, luminescence was measured as a surrogate indicator of cell viability using a PHERAstar FSX microplate reader (BMG LABTECH, Cary, NC) [ 21 , 22 ]. Data Analysis . Luminescence measurements from the screen were exported as comma separated values (CSV) files and imported into custom Excel spreadsheets (Microsoft, Redmond, WA) for analysis. The raw luminescence data were evaluated for quality control, filtered for outliers, and converted to percent viability by normalizing to the DMSO (vehicle-treated) control. Concentration-response data were fit to the four-parameter logistic equation using the Solver Add-In in Excel. The Bliss independence model states that if two drugs have independent activities, then the viability for the combination is equal to the product of the viability of the two single agents [ 22 , 23 ]. Synergy between two compounds was indicated by a lower observed percent viability than predicted by the Bliss independence model, whereas antagonism was indicated by a greater observed percent viability than predicted. The mean and statistical significance of Bliss independence scores for each drug combination-model across all concentrations and biological replicates were evaluated [ 23 ]. Response surface maps were generated using the MATLAB web application where blue indicates synergy and red indicates antagonism. Data Availability . All data are accessible via the PubChem BioAssay public database (AID 1918931; AID1918932; AID1918933; AID1918930; AID1918934; AID1918935; AID1918936; AID1918937; AID1918938; AID8939; AID1918942; AID8944; AID1918943; AID1918945; AID1918946; AID1918947; AID1918949; AID1918948; AID8950; AID1918951; AID1918952; AID1918953; AID1918954; AID1918955; AID1918957; AID1918958; AID1918940; AID1918956; AID8941; AID2060627; AID 2060626; AID 2060625; AID 2060624; AID 2060623; AID 2060613; AID 2060622; AID 2060619; AID 2060621; AID 2060620; AID 2060616; AID 2060604; AID 2060603; AID 2060618; AID 2060617; AID 2060615; AID 2060612; AID 2060614; AID 2060610; AID 2060611; AID 2060602; AID 2060599; AID 2060609; AID 2060601; AID 2060608; AID 2060607; AID 2060606; AID 2060605; AID 2060600 ( Table 4 ). RESULTS Single agent concentration response data for two investigational CLK inhibitors cirtuvivint and CC-671, and an investigational LSD1 inhibitor iadademstat, are shown in Figure 1 . The compounds were tested 26 human tumor cells lines grown as mct-spheroids in 9-point concentration response at concentrations spanning 4-logs with an exposure time of 7 days. Cirtuvivint was the most potent cytotoxin with IC 90 concentrations between 0.2 to 10 µM. The LSD-1 inhibitor iadademstat was assessed in mct-spheroids in 29 cell lines including PDMR lines and established lines. The most responsive lines were the NCI-H211 SCLC, two triple-negative breast cancer lines MDA-MB-231 and MDA-MB-468, a pancreatic carcinoma line 292921-168-R-J2, and an ovarian carcinoma line 556581-035-R-J1; however, only the NCI-H211 mct-spheroids reached an IC 50 at 7.5 µM. Iadademstat was the least cytotoxic and reached an IC 50 concentration only in the MDA-MB-468 cell line at 10 µM, the highest concentration tested. Cirtuvivint, CC-671 and iadademstat were tested in combination with anticancer drugs and investigational agents in complex mct-spheroids composed of human tumor cells with known genetic alterations, HUVEC and hMSC cells. The drugs and investigational agents tested are listed in Table 1 . The genetic variants for key genes in the tumor cell lines are shown on Table 2 . Drugs and investigational agents were tested at concentrations beginning at the clinical Cmax concentration or at 10 µM, if the clinical Cmax was not established, decreasing in half-log increments for 6 concentrations. The KRAS G12D selective inhibitor MRTX-1133 was assessed in combination with cirtuvivint in four PDMR lines harboring the KRAS G12D mutation and the 616215-338-R-J1 colon carcinoma which harbors a KRAS G12S mutation ( Figure 2 ) [ 24 ]. The PDMR lines with KRAS G12D were among the most responsive to MRTX-1133 as a single agent with 377384-186-R-J1 pancreatic carcinoma mct-spheroids being most responsive. Simultaneous combination of cirtuvivint and MRTX-1133 produced primarily additive cytotoxicity with a few regions of great-than-additive cytotoxicity in the 186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma, 377384-186-R-J1 pancreatic carcinoma and 242566-281-R-J2 pancreatic carcinoma mct-spheroids with up to 2.5-3-logs of cell killing. The 616215-338-R-J1 colon carcinoma harboring a KRAS G12S mutation was also responsive to the combination of cirtuvivint and MTRX-1133. The response of the same five tumor mct-spheroids was assessed after 7-days exposure to CC-671 with MRTX-1133 ( Figure 2 ). Tumor cell killing was greatest in the 377384-186-R-J1 pancreatic carcinoma complex mct-spheroids reaching 2-logs which was additive by the Bliss independence calculation. Greater-than-additive cell killing was evident under the same conditions for the 377384-186-R-J1 pancreatic carcinoma, the186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma mct-spheroids. The maximal tumor cell killing achieved with CC-671 and MRTX-1133 in the 377384-186-R-J1 pancreatic carcinoma, the 186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma and 616215-338-R-J1 colon carcinoma mct-spheroids was 1-log. Moving down-stream of RAS, the simultaneous combination of cirtuvivint and the pan-PI3K inhibitor copanlisib was examined in five PDMR cell lines, the 186277-243-T-J2 colon carcinoma, the 168753-222-R-J1 bladder carcinoma, 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma mct-spheroids with a 7-day exposure ( Figure 3A ) [ 25 ]. The 168753-222-R-J1 bladder carcinoma mct-spheroids were more responsive to copanlisib as a single agent than were the 186277-243-T-J2 colon carcinoma mct-spheroids. The tumor cell killing was primarily additive in both tumor lines reaching 2-logs for the 186277-243-T-J2 colon carcinoma mct-spheroids and 3-logs for the168753-222-R-J1 bladder carcinoma mct-spheroids. The 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma mct-spheroids with a 7-day exposure were similarly responsive to the combination of copanlisib and cirtuvivint with cell killing reaching 2- to -3-logs. The same five PDMR cell lines were exposed to CC-671 in simultaneous combination with copanlisib ( Figure 3A ). The combination of CC-671 with copanlisib was less cytotoxic than the combination of cirtuvivint with copanlisib in each of the five cell lines tested as mct-spheroids. The combination produced maximal cytotoxicity in the 168753-222-R-J1 bladder carcinoma mct-spheroids with additive to greater-than additive cell killing reaching 2-logs while the same combination produced less than 1-log of cell kiliing in the 485368-065-R4-J2 pancreatic carcinoma mct-spheroids. The simultaneous combination of cituvivint and the PI3Ka selective inhibitor inavolisib in 186277-243-T-J2 colon carcinoma mct-spheroids resulted in additive to greater-than-additive cytotoxicity reaching a maximum to 2-logs ( Figure 3B ) [ 26 ]. As determined by the Bliss independence calculation the combination of cirtuvivint and inavolisib produced additive cell killing in the 168753-222-RJ1 bladder carcinoma mct-spheroids reaching 3-logs at the 2 highest concentrations of cirtuvivint across the concentration range of inavolisib. Greater-than-additive cell killing was seen with inavolisib in simultaneous combination with CC-671 in mct-spheroids grown from 947758-054-R-J2 colon carcinoma cells and 186277-243-T-J2 colon carcinoma cells ( Figure 3B ). Neither 947758-054-RJ2 colon carcinoma mct-spheroids nor 186277-243-TJ2 colon carcinoma mct-spheroids was very responsive to CC-671 reaching 62% and 70% cell killing, respectively. The combination of CC-671 and inavolisib reached nearly 2-logs of cell killing in both lines with more evidence of greater-than-additive cell killing occurring in the 947758-054-R-J2 colon carcinoma mct-spheroids. Inavolisib was not effective in the 947758-054-R-J2 colon carcinoma mct-spheroids; however, greater-than-additive killing occurred over the 6x6 concentration matrix, the same was true of the combination of CC-671 and inavolisib in the 186277-243-TJ2 colon carcinoma mct-spheroids albeit the magnitude was less. Overall, the combination of CC-671 and inavolisib reached 1.5-logs of cell killing in both tumor lines. As a single agent the XPO1 inhibitor eltanexor, resulted in 1- to 2-logs of cytotoxicity in mct-spheroids after a 7-day exposure [ 27 , 28 ]. Five cell lines were selected to highlight the results from the combination of cirtuvivint and eltanexor ( Figure 4 ). The simultaneous combination of cirtuvivint with eltanexor produced additive to greater-than-additive killing of 616215-338-R-J1 colon carcinoma mct-spheroids. While greater-than-additive cytotoxicity of the combination was observed at moderate concentrations of eltanexor and lower concentrations of cirtuvivint, cell killing of 2- to 3-logs was observed at the higher concentrations of both agents. The simultaneous combination of cirtuvivint and eltanexor produced greater-than-additive cytotoxicity at moderate concentrations of both agents in the 996289-038-R-J1 colon carcinoma mct-spheroids reaching 2.5-logs. The simultaneous combination of cirtuvivint and eltanexor was additive in the 876135-273-R-J2 melanoma, the 648629-189-R-J1 bladder carcinoma and 377384-186-R-J1 pancreatic carcinoma. Additive to less-than additive tumor cell killing occurred over a wide concentration range of both CC-671 and eltanexor in 616215-338-R-J1 colon carcinoma and the 996289-038-R-J1 colon carcinoma mct-spheroids reaching a maximum of about 1.5-logs. The greatest depth of tumor cell killing was observed in the 876135-273-R-J2 melanoma mct-spheroids reaching 3-logs at the two highest concentrations of CC-671 and eltanexor ( Figure 4 ). The DNA-PK inhibitor peposertib was studied in combination with the CLK inhibitor cirtuvivint or with the LSD-1 inhibitor iadademstat ( Figure 5A ) [ 29-31 ]. While peposertib as a single agent was not highly effective in the five PDMR cell lines highlighted, 1566681-154-R-J1 melanoma, 233499-124-R-J3 and 616215-338-R-J1 colon carcinomas, 324938-238-R-1 and 565232-114-T-J1 bladder carcinomas, the combination of peposertib and cirtuvivint resulted in 2- to 3-logs of cell killing in each of the 5 lines grown as mct-spheroids. In contrast, the combination of peposertib with the LSD-1 inhibitor iadademstat resulted in sub-additive to additive cell killing in the five PDMR lines highlighted, 186277-243-T-J2 and 233499-124-R-J3 colon carcinomas, 324938-238-R-1 bladder carcinoma, 743899-274-T renal cell carcinoma and 521955-158-R2-J5 pancreatic carcinoma ( Figure 5A ). SN-38 is the active metabolite of the prodrug irinotecan, that acts, like irinotecan, by inhibiting topoisomerase I, an enzyme induces a single strand break in DNA to relax the DNA during replication [ 32, 33 ]. SN-38 was tested at concentrations up to 1µM during the 7-day exposure period ( Figure 5B ). At the lower concentrations of cirtuvivint and moderate to high concentrations of SN-38 marked greater-than-additive tumor cell killing with Bliss additivity scores up to 66 for the 616215-338-R-J1 colon carcinoma, 58 for the 233499-124-R-J3 colon carcinoma, 40 for the 565232-114-T-J1 bladder carcinoma, and 21 for the 186277-243-T-J2 colon carcinoma while, the combination of cirtuvivint and SN-38 produced additive cytotoxicity due to the sensitivity of the 186277-243-T-J2 mct-spheroid to SN-38 which killed 1-log of cells as a single agent ( Figure 5B ). By comparison, the combination of iadademstat and SN-38 produced less-than-additive to additive cell killing over the iadademstat and SN-38 concentrations tested. The histone deacetylase inhibitor entinostat was tested in combination with cirtuvivint and iadademstat and the results from five PDMR human tumor cell lines grown as mct-spheroids are shown in Figure 6A [ 34, 35 ]. The combination of entinostat with cirtuvivint were additive in the five cell lines highlighted over the concentration ranges of the drugs tested with a 7-day exposure time. A similar result was obtained with the combination of iadademstat with entinostat with the five PDMR cells lines grown as mct-spheroids producing less-than-additive to additive cytotoxicity. Combinations of cirtuvivint and iadadematat with the PARP1 inhibitor olaparib in five of the PDMR tumor cell lines grown as mct-spheroids resulted in the combination producing sub-additive to additive cytotoxic effects in the 324938-238-R-1 and 565232-114-T-J1 bladder carcinomas and additive to greater-than additive cytotoxicity in the 186277-243-T-J2 and 616215-338-R-J1 colon carcinomas ( Figure 6B )[ 36 ]. The combination of iadademstat with olaparib resulted in little cytotoxicity with combinations just reaching an IC 50 with the highest concentration of both drugs. Iadademstat was tested with the NEDD8-activating enzyme (NAE) inhibitor pevonedistat ( Figure 7 ). Pevonedistat prevents the activation of cullin-RING E3 ligases thereby blocking the ubiquitination and proteasomal degradation of cellular proteins causing a build-up of proteins leading to cell death [ 37-41 ]. The K-562 leukemia was responsive to pevonedistat reaching 1 log of cytotoxicity at the highest concentration (3 mM) tested. There was an iadademstat concentration dependent increase in cytotoxicity with iadademstat and pevonedistat reaching 2-logs at 3 mM pevonedistat ( Figure 7 ). Of the two PDMR pancreatic carcinoma lines, the less responsive the 521955-158-R2-J5 pancreatic carcinoma mct-spheroids reached >1-log, while the 292921-186-R-J2 pancreatic carcinoma mct-spheroids reached 2-logs of cell killing at higher pevonedistat concentrations. The OVCAR-5, and NCI/ADR-RES ovarian carcinoma mct- spheroids were responsive to pevonedistat reaching 1-log at 3mM pevonedistat. Combination of pevonedistat with iadademstat did not increase OVCAR-5 or NCI/ADR-RES mct-spheroid killing compared with pevonedistat alone. TAK-243 is an inhibitor of the (UAE). UAE is the primary E1 enzyme regulating the ubiquitin conjugation cascade [ 42-43 ]. The binding of TAK-243 to UAE prevents protein ubiquitination resulting in protein accumulation (proteotoxic stress) and leading to cell death. The K-562 leukemia was responsive to TAK-243 with 3-logs of cytotoxicity at the highest concentration of TAK-243 (0.3 mM) tested ( Figure 7 ). Iadademstat with TAK-243 resulted in an iadademstat concentration dependent increase in K-562 leukemia cell cytotoxicity at the lower concentrations of TAK-243 compared with TAK-243 alone. Two of the PDMR pancreatic carcinoma, 292921-186-R-J2 and 521955-158-R2-J5, were as responsive to TAK-243 as was the K-562 leukemia reaching 3-logs of cytotoxicity. Iadademstat with TAK-243 increase in cytotoxicity in the two pancreatic carcinoma mct-spheroids compared with TAK-243. TAK-243 and iadademstat produced a modest increase in cytotoxicity. The PDMR 556581-035-R-J1 ovarian carcinoma was highly responsive to TAK-243 reaching 3-logs of cytotoxicity. Iadademstat with TAK-243 increased cytotoxicity compared with TAK-243 alone at the mid-range concentrations. The NCI/ADR-RES ovarian carcinoma mct-spheroids were responsive to TAK-243 reaching 2-logs of cytotoxicity. Iadademstat with TAK-243 was less cytotoxic than TAK-243 as a single agent in the NCI/ADR-RES cell line. The OVCAR-5 cell line was responsive to TAK-243 reaching nearly 2-logs of cell killing. The combination of iadademstat and TAK-243 was modestly more cytotoxic than TAK-243. DISCUSSION Most genes with multiple introns and exons undergo alternative splicing to generate multiple mRNAs which are then translated into the diversity of proteins making up cellular proteins required for differentiation, development, and cell death in a process performed by spliceosomes, highly complex structures made up of approximately 300 proteins and RNA [ 45-47 ]. The Cancer Genome Atlas (TCGA) indicates that many solid tumors and hematologic malignancies deregulate DYRK1A. The pan-CLK/DYRK inhibitor cirtuvivint can cause programmed cell death at concentrations which inhibit the accumulation of phosphorylated SR proteins and alter splicing decreasing cellular proliferation in hematologic PDXs [ 45 ]. Cirtuvivint inhibits spliceosome associated CLK kinases especially SRSF5/6, thus, providing indirect inhibition of Wnt signaling resulting in antitumor activity [ 46 ]. Approximately 90% of colorectal cancers have mutations in the Wnt/β-catenin signaling pathway and aberrant Wnt signaling often occurs in gastric, pancreatic, breast and other cancers [ 46 ]. CC-671 is a potent and selective inhibitor of both TTK (human protein kinase monopolar spindle 1 [hMps1]) and CDC like kinase 2 (CLK2). A protein docking analysis indicated that CC-671 has high binding affinity to the drug-binding site of ABCG2 [ 47 ]. While dysregulation and alteration in pre-mRNA splicing is a recognized therapeutic target in hematologic malignancies, targeting pre-mRNA splicing has only been pursued recently for solid tumors. Pre-mRNA splicing modulation followed by PARP inhibition or chemotherapy in BRCA-mutant breast and ovarian cancers characterized by a “BRCA-ness” phenotype of dysfunctional homologous DNA repair [ 48 ]. Spliceosome-associated SR protein kinases SRPKs, CLKs, and NEK2 are altered in many cancers [ 49 ]. The CLK kinase family which includes CLK1-4, in conjunction with SRPK kinases adjust phosphorylation of SR proteins to modulate alternative splicing. CLK kinase activity changes are associated with cancer development and progression. Phosphorylation of SR proteins impact their subcellular localization, association with the spliceosome complex, and splicing activity[ 49 ].SRSF5 and SRSF3 were reported to be overexpressed in oral squamous cell carcinoma (OSCC), and necessary for OSCC cell proliferation, cell cycle progression, and in vivo tumor formation. SRSF5-7 were found to be upregulated in small cell lung cancer (SCLC) and NSCLC tissues, and knockdown of SRSF5-7 in SCLC cell lines showed a significant decrease in proliferation [ 49 ]. Epigenetic mechanisms control gene expression patterns without change in DNA sequence. Histones, DNA binding proteins involved in regulation of nucleosome function, are subject to methylation, acetylation, phosphorylation, and ubiquitination. The methylation and demethylation of lysine residues on histone tails are post-translational protein modifications which control gene expression. The KDM (K=lysine) demethylase gene family includes 20 KDMs. KDM1s utilize a flavin adenine dinucleotide cofactor to demethylate methylated lysine substrates. KDM1A regulates many aspects of cell biology including self-renewal, differentiation, and stem cell pluripotency [ 50 ]. The protein encoded by the KDM1A gene is LSD1 which removes mono- and dimethyl groups from histone H34K and other chromatin-associated proteins. Two ways epigenetic therapies act as anticancer therapies are repression of oncogene function or activation of tumor-suppressor genes [ 51 ]. LSD1 is overexpressed in many proliferative diseases including hematological, lung, breast, and prostate cancers. Iadademstat, an irreversible LSD1 inhibitor, is in clinical development [ 52-54 ]. Several LSD1 inhibitors have completed Phase 1 clinical trial and have moved on to Phase 2 studies [ 55 , 56 ]. Pevonedistat interferes with the function of the proteasome pathway blocking NAE. The PDMR 292921-168-R-J2 pancreatic carcinoma mct-spheroids was most responsive to pevonedistat reaching 2-logs of cytotoxicity and the K-562 leukemia, the PDMR 521955-158-R-J5 pancreatic carcinoma and the ovarian carcinoma lines OVCAR-5 and NCI/ADR-RES mct-spheroids reached 1-log of cytotoxicity upon exposure to pevonedistat for 7 days. The combination of iadademstat and pevonedistat resulted in increased cytotoxicity in the K-562 leukemia and the PDMR 556581-035-R-J1 ovarian carcinoma compared with single agent pevonedistat ( Figure 7 ). TAK-243 was markedly cytotoxic as a single agent in the K-562 leukemia, in 2 of 3 PDMR pancreatic carcinomas, 292921-168-R-J2 and 521955-158-R-J5, and the PDMR 556581-035-R-J1 ovarian carcinoma resulting in 3-logs of cytotoxicity at the highest concentration (0.3 mM) tested. There was little increase in response with iadademstat and TAK-243. A first-in-human phase 1 iadademstat clinical study was conducted in relapsed refractory acute leukemia enriched with MLL/KMT2A-rearranged acute myeloid leukemia patients with most having MLL-translocation disease. The pharmacokinetic data indicate that the iadademstat clinical Cmax concentration was 0.116-0.182 nM, a concentration below the concentration range of 0.1-10 µM in the current study [ 57 , 58 ]. Some patients with a molecular response to treatment with iadademstat showed blast cell differentiation, but no clinical responses were seen. In the current screen of 29 cell lines and 25 drugs and investigational agents indicate that response is highly cell line dependent. Although genetic marker(s) that might correlate with response to the combination regimens were sought no clear marker(s) emerged. Declarations Funding: This project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261201500003I. Author Contribution BAT, NPC and TSD wrote the main manuscript text and BAT and TS prepared figures 1-7. All authors reviewed the manuscript. Data Availability All data are available in PubChem as shown in the manuscript. References Bradley RK, Anczuków O. RNA splicing dysregulation and the hallmarks of cancer. Nature Rev Cancer 2023; 23: 135–55. Aubol BE, Wozniak JM, Fattet L, Gonzalez DJ, Adams JA. CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly. Proc Natl Acad Sci 2021; 118: e2018251118. Yoshimi A, Abdel-Wahab O. Molecular pathways: understanding and targeting mutant spliceosomal proteins. Clin Cancer Res 2017; 23: 336-41. Moyano PM, Nemec V, Paruch K. Cdc-like kinases (CLKs): biology, chemical probes, and therapeutic potential. Int J Mol Sci 2020; 21: 7549. Song M, Pang L, Zhang M, Qu Y, Laster KV, Dong Z. Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases. Sig Transduc Targ Therap 2023; 8:148. Corr BR, Moroney MR, Woodruff E, Watson ZL, Jordan KR, Danhorn T, Bailey C, Wolsky RJ, Bitler BG. Combination CDC-like kinase inhibition (CLK)/Dual-specificity tyrosine-regulated kinase (DYRK) and taxane therapy in CTNNB1 -mutated endometrial cancer. bioRxiv: posted April 6, 2023. Riggs JR, Nagy M, Elsner J, Erdman P, Cashion D, Robinson D, Harris R, Huang D, Tehrani L, Deyanat-Yazdi G, Narla RK, Peng X, Tran T, Barnes L, Miller T, Katz J, Tang Y, Chen M, Moghaddam MF, Bahmanyar S, Pagarigan B, Delker S, LeBrun L, Chamberlain PP, Calabrese A, Canan SS, Leftheris K, Zhu D, Boylan JF. The discovery of a dual TTK protein kinase/CDC2-like kinase (CLK2) inhibitor for the treatment of triple negative breast cancer initiated from a phenotypic screen. J Med Chem 2017; 60: 8989-9002. Zhu D, Xu S, Deyanat-Yazdi G, Peng SX, Barnes LA, Narla RK, Tran T, Mikolon D, Ning Y, Shi T, Jiang N, Raymon HK, Riggs JR, Boylan JF. Synthetic lethal strategy identifies a potent and selective TTK and CLK1/2 inhibitor for treatment of triple-negative breast cancer with a compromised G1–S checkpoint. Mol Cancer Ther 2018; 1: 17: 27–38. McGrath J, Trojer P. Targeting histone lysine methylation in cancer. Pharmacol Ther 2015; 150: 1-22. Schmidt DMZ, McCafferty DG. Trans-2-phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochem 2007; 46: 4408-16. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA , et al . Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004; 119: 941-53. McGrath JP, Williamson KE, Balasubramanian S, Odate S, Arora S, Hatton C, Edwards TM, Thomas O'Brien T, Magnuson S, Stokoe D, Daniels DL, Bryant BM, Patrick Trojer P. Pharmacological inhibition of the histone lysine demethylase KDM1A suppresses the growth of multiple acute myeloid leukemia subtypes. Cancer Res 2016; 76: 1975-88. Wang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine GG, et al . Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 2007; 446: 882-7. Maes T, Carceller E, Salas J, Ortega A, Buesaet C. Advances in the development of histone lysine demethylase inhibitors. Curr Opin Pharmacol 2015; 23: 52-60. Harris WJ , Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y, Ciceri F, Blaser JG, Greystoke BF, Jordan AM, Miller CJ, Donald J. Ogilvie DJ, Somervaille TCP. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 2012; 21: 473–87. Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, Casero RA, Marton L, Woster P, Minden MD, Dugas M, Wang JCY, Dick JE, Müller-Tidow C, Petrie K, Zelent A. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nature Med 2012; 18: 605-11. Maes T, Tirapu I, Mascaró C, Ortega A, Estiarte A, Castro-Palomino NV, Arjol CB, Guido Kurzet G. Preclinical characterization of a potent and selective inhibitor of the histone demethylase KDM1A for MLL leukemia. J Clin Oncol 2013; 31: e13543. Smitheman K, Cusan M, Liu Y, Butticello M, Pappalardi M, Foley J, Federowicz K, Van Aller G, Kasparec J, Tian X, Suarez D, Schneck J, Carson J, McDevitt P, Ho T, McHugh C, Miller W, Armstrong S, Hann C, Johnson N, Kruger RG, Mohammad HP, Shekhar Kamat S. Inhibition of LSD1 for the treatment of cancer. Cancer Res 2015; 75: 3513. Augert A, Eastwood E, Ibrahim AH, Wu N, Grunblatt E, Basom R , et al . Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition. Sci Signal 2019; 12: 10.1126/scisignal.aau2922. Morris J, Kunkel MW, White SL, Wishka DG, Lopez OD, Bowles L, et al. Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems-based Resource. Mol Cancer Ther 2023;22:1270-9. Kaur G, Evans DM, Teicher BA, Coussens NP. Complex Tumor Spheroids, a Tissue-Mimicking Tumor Model, for Drug Discovery and Precision Medicine. SLAS Discov 2021 ;26:1298-314. Dexheimer TS, Coussens NP, Silvers T, Wright J, Morris J, Doroshow JH, Teicher BA. Multicellular complex tumor spheroid response to DNA repair inhibitors in combination with DNA-damaging drugs. Cancer Res Commun 2023; 3(8): 1648-61. Bliss CI. The Toxicity of Poisons Applied Jointly. Annals of Applied Biology 1939;26:585-615. Wang XL, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, et al. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS Inhibitor. J Med Chem 2022; 65: 3123-33. Skanland SS, Okkenhaug K, Davids MS. PI3K inhibitors in hematology: when one door closes. Clin Cancer Res 2024; 30: 3667–75. Song KW, Edgar KA, Hanan EJ, Hafner M, Oeh J, Merchant M, Sampath D, Nannini MA, Hong R, Phu L, Forrest WF, Stawiski E, Schmidt S, Endres N, Guan J, Wallin JJ, Cheong J, Plise EG, Lewis Phillips GD, Salphati L, Heffron TP, Alan G. Olivero AG, Malek S, Staben ST,Kirkpatrick DS, Dey A, Friedman LS. RTK-dependent inducible degradation of mutant PI3Ka drives GDC-0077 (inavolisib) efficacy. Cancer Discov 2022;12: 204–19. Camilli S, Lockey R, Kolliputi N. Nuclear export inhibitors selinexor (KPT-330) and eltanexor (KPT-8602) provide a novel therapy to reduce tumor growth by induction of PANoptosis. Cell Biochem Biophys 2023; 81: 421–26. Binder AF, Walker CJ, Mark TM, Baljevic M Impacting T-cell fitness in multiple myeloma: potential roles for selinexor and XPO1 inhibitors. Front Immunol 2023; 14: 1275329. Gordhandas SB, Manning-Geist B, Henson C, Iyer G, Gardner GJ, Sonoda Y, Moore KN, Aghajanian C, Chui MH, Grisham RN. Preclinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer. Scientific Reports 2022; 12: 974. van Bussel MTJ, Awada A, de Jonge MJA, Mau-Sørensen M, Nielsen D, Schöffski P, Verheul HMW, Sarholz B, Berghoff K, El Bawab S, Kuipers M, Damstrup L, Diaz-Padilla I, Schellens JHM. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumors. Brit J Cancer 2021; 124: 728–35. Samuels M, Falkenius J, Bar-Ad V, Dunst J, Triest B, Yachnin J, Rodriguez-Gutierrez A, Kuipers M, You X, Sarholz B, Locatelli G, Becker A, Troost EGC. A Phase1studyof the DNA-PK inhibitor peposertib in combination with radiation therapy with or without cisplatin in patients with advanced head and neck tumors. Int J Radiat Oncol Biol Phys 2024; 118: 743-56. Jandu H, Aluzaite K, Fogh L, Thrane SW, Noer JB, Proszek J, Do KN, Hansen SN, Damsgaard B, Nielsen SL, Stougaard M, Knudsen BR, Moreira J, Hamerlik P, Gajjar M, Smid M, Martens J, Foekens J, Pommier Y, Brünner N, Schrohl AS, Stenvang J. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. BMC Cancer 2016;16:34. Jensen NF, Agama K, Roy A, Smith DH, Pfister TD, Rømer MU, Zhang HL, Doroshow JH, Knudsen BR, Stenvang J, Brünner N, Pommier Y. Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations. J Exp Clin Cancer Res 2016;35:56. Lian B, Chen X, Shen K. Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer. Front Immunol 2023;14:1164514. Wang C, Lin Y, Zhu H, Zhou Y, Mao F, Huang X, Sun Q, Li C. Efficacy and Safety Profile of Histone Deacetylase Inhibitors for Metastatic Breast Cancer: A Meta-Analysis. Front Oncol. 2022;12:901152. Awasthi S, Dobrolecki LE, Sallas C, Zhang X, Li Y, Khazaei S, Ghosh S, Jeter CR, Liu J, Mills GB, Westin SN, Lewis MT, Peng W, Sood AK, Yap TA, Yi SS, McGrail DJ, Sahni N. UBA1 inhibition sensitizes cancer cells to PARP inhibitors. Cell Rep Med. 2024; 5:101834. Soucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 2009; 458: 732–6. Soucy TA, Smith PG, Rolfe M. Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer. Clin Cancer Res 2009; 15: 3912–16. Swords RT, Kelly KR, Smith PG, et al. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood 2010; 115: 3796–800. Ferris J, Espona-Fiedler M, Hamilton C, Holohan C, Crawford N, McIntyre AJ, Roberts JZ, Wappett M, McDade SS, Daniel B. Longley DB, Coyle V. Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer. Cell Death Discov 2020, 6:61. Hyer ML, Milhollen MA, Ciavarri J, Fleming P, Traore T, Sappal D, Huck J, Shi J, Gavin J, Brownell J, Yang Y, Stringer B, Griffin R, Bruzzese F, Soucy T, Duffy J, Rabino C, Riceberg J, Hoar K, Lublinsky A, Menon S, Sintchak M, Bump N, Pulukuri SM, Langston S, Tirrell S, Kuranda M, Veiby P, Newcomb J, Li P, Wu JT, Powe J, Dick LR, Greenspan P, Galvin K, Manfredi M, Claiborne C, Amidon BS, Bence NF. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat Med 2018; 24: 186-93. Arakawa Y, Jo U, Kumar S, Sun NY, Elloumi F, Thomas A, Roper N, Varghese DG, Takebe N, Zhang X, Ceribelli M, Holland DO, Beck E, Itkin Z, McKnight C, Wilson KM, Travers J, Klumpp-Thomas C, Thomas CJ, Hoang CD, Hernandez JM, Del Rivero J, Pommier Y. Activity of the ubiquitin-activating enzyme Inhibitor TAK-243 in adrenocortical carcinoma cell lines, patient-derived organoids, and murine xenografts. Cancer Res Commun 2024; 4:834-48. Wu Z, Yang Y, Lei Z, Narayanan S, Wang J, Teng Q, Murakami M, Ambudkar SV, Ping F, Chen Z. ABCB1 limits the cytotoxic activity of TAK-243, an inhibitor of the ubiquitin-activating enzyme UBA. Front Biosci (Landmark Ed). 2022; 27:5. Bonner EA, Lee SC. Therapeutic targeting of RNA splicing in cancer. Genes 2023; 14: 1378. Tam BY, Chiu K, Chung H, Bossard C, Nguyen JD, Creger E, Eastman BW, Mak CC, Ibanez M, Ghias A, Cahiwat J, Do L, Cho S, Nguyen J, Deshmukh V, Stewart J, Chen CW, Barroga C, Dellamary L, KC SK, Phalen TJ, Hood J, Cha S, Yusuf Yazici Y. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Letters 2020; 473: 186-97. Wu ZX, Yang Y, Wang G, Wang JQ, Teng QX, Sun L, Lei ZN, Lin L, Chen ZS, Zou C. Dual TTK/CLK2 inhibitor, CC-671, selectively antagonizes ABCG2-mediated multidrug resistance in lung cancer cells. Cancer Sci 2020; 111: 2872–82. Wheeler EC, Martin BJE, Doyle WC, Neaher S, Conway CA, Pitton CN, Gorelov RA, Donahue M, Jann JC, Abdel-Wahab O, Taylor J, Seiler M, Buonamici S, Pikman Y, Garcia JS, Belizaire R, Adelman K, Tothova Z. Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML. Sci Transl Med 2024; 16: eade2774. Murphy AJ, Li AH, Li P, Sun H. Therapeutic targeting of alternative splicing: A new frontier in cancer treatment. Front Oncol 2022; 12: 868664. Kurmasheva RT, Erickson SW, Han R, Teicher BA, Smith MA, Roth M, Gorlick R, Houghton PJ. In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). Pediatr Blood Cancer 2021; 68: e29304. Tremblay D, Mesa R. Novel treatments for myelofibrosis: beyond JAK inhibitors. Int J Hematol 2022; 115: 645-58. Sacilotto N, Dessanti P, Lufino MMP, Ortega A, Rodríguez-Gimeno A, Salas J, Maes T, Buesa C, Mascaró C, Soliva R. Comprehensive in vitro characterization of the LSD1 small molecule inhibitor class in oncology. ACS Pharmacol Transl Sci 2021; 4: 1818−34. Soldi S, Halder TG, Weston A, Thode T, Drenner K, Lewis R, Kaadige MR, Srivastava S, Ampanattu SD, del Villar RR, Lang J, Vankayalapati H, Weissman B, Trent JM, Hendricks WPD, Sharma S.The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-Non-Fermentable (SWI/SNF) complex mutated ovarian cancer. PLoS ONE 2020; 15: e0235705. Hodges S, Cooney J. Novel lysine-specific histone demethylase 1 inhibitor in acute myeloid leukemia transformed from essential thrombocythaemia. Cancer Rep 2022; 5: e1588. Fang Y, Liao G, Bin Yu B. LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol 2019; 12:129 . Clement Agboyibor C, Dong J, Effah CY, Drokow EK, Pervaiz W, Liu HM. LSD1 as a biomarker and the outcome of its inhibitors in the clinical trial: the therapy opportunity in tumors. J Oncol 2021: .5512524 Hiatt JB, Sandborg H, Garrison SM, Arnold HU, Liao SY, Norton JP, Friesen TJ, Wu F, Sutherland KD, Rienhoff Jr. HY, Martins R, Houghton AM, Srivastava S, MacPherson D. Inhibition of LSD1 with bomedemstat sensitizes small cell lung cancer to immune checkpoint blockade and T cell killing. Clin Cancer Res 2022; 28: 4551-64. Salamero O, Montesinos P, Willekens C, Pérez-Simón JA, Pigneux A, Récher C, Popat R, Carpio C, Molinero C, Mascaró C, Vila J, Arévalo MI, Maes T, Buesa A, Bosch F, Somervaille TCP. First-in-human Phase I study of iadademstat (ORY-1001): a first-in-class lysine-specific histone demethylase 1A inhibitor, in relapsed or refractory acute myeloid leukemia. J Clin Oncol 2020; 38: 4260–73. Tables Table 1 . Drugs and investigational agents for pidnarulex (CX-5461), APTO-253(LOR-253), BRACO-19, iadademstat, cirtuvivint and CC-671 combination mct-spheroid screens. Drug or Invest Ag NSC # MW Clin Cmax (10 uM default) Target Cirtuvivint 835563 427.5 3 µM CLKs/DYRKs CC-671 805746 512.6 10 µM CLK2/TTK Iadademestat 806812 230.35 10 µM LSD1 (KDM1A) 5-Fluorouracil 19893 130.1 426 µM Thymidylate synthase Abemaciclib 763073 506 0.59 µM CDK4/6 Adagrasib 831453 604.12 3 µM KRAS G12C Adavosertib (MK-1775) 754352 500.6 10 µM WEE-1 Alisertib 759677 519 10 µM Aurora Kinase ART-558 835418 418.4 10 µM POLQ Aza-T-dCyd 777586 244.27 0.3 µM DNMT1 AZD-1390 803789 477.6 10 µM ATM BAY2416964 825713 378.8 10 µM AhR inhibitor Belinostat 758774 318 134 µM HDAC Bortezomib 756655 394 0.312 µM Proteasome Camonsertib 841442 410.5 10 µM ATR Carboplatin 241240 371.3 135 µM DNA crosslinking Ceralasertib 780249 412.5 10 µM ATR Cisplatin 119875 300 14.4 µM DNA Copanlisib 816437 480.53 0.964 µM AKT α/δ CPI-455 825282 314.77 10 µM KDM5 Dacitabine 127716 228 0.323 µM DNMT1 Doxorubicin 123127 544 6.73 µM TopII/DNA intercalator Elimusertib 800525 375.4 10 µM ATR Eltanexor 794443 428.3 10 µM XPO1 Entinostat 756642 376.4 10 µM HDAC Eribulin 707389 730 0.508 µM Tubulin Etoposide 141540 588.6 33.4 µM TopII inhibitor Gemcitabine 613327 263 89.3 µM Antimetabolite/ Inavolisib 800729 407.4 10 µM PIK3CA, PI3Ka Ixazomib 758254 517 0.118 µM Proteasome KSQ-4279 (R07623066) 840948 534.54 10 µM USP1 MRTX-1133 836407 600.63 10 µM KRAS G12D Olaparib 753686 434 13.1 µM PARP Osimertinib 779217 500 0.126 µM EGFR Oxaliplatin 266046 397 4.96 µM DNA crosslinker Paclitaxel 125973 854 4.27 µM Tubulin stabilizer Panobinostat 761190 349 0.082 µM HDAC Peposertib 802822 481.1 10 µM DNA-PK Pevonedistat 761192 443.5 10 µM NAE (NEDD8) R306465 773264 413.5 10 µM HDAC Selinexor 780203 443.3 1.53 µM CRM1 SN-38 673596 392.4 - TopI inhibitor Sotorasib 818433 561 10 µM KRAS G12C TAK-243 785004 519.5 0.3 µM UAE Talazoparib 767125 380.4 0.043 µM PARP Tapotoclax 804041 613.2 10 µM MCL-1 Tazemetostat 777109 572.75 1.45 µM EZH2 Topotecan 609699 421 0.015 µM TopI inhibitor TP-3654 805149 418.5 10 µM PIM-1 Vemurafenib 761431 490 127 µM BRAF V600E Venetoclax 766270 468 4.48 µM BCL-2 Table 2 . Tumor cell lines tested as complex spheroids (including endothelial cells and mesenchymal stem cells) for response to cirtuvivint, CC-671 or iadademstat alone and in simultaneous combination with the compounds in Table 1 . The disease type and key genetic aberrations for each line are shown. Some lines are from the DCTD PDMR (https://pdmr.cancer.gov/). Cell Line Disease Key Mutations 138582-337-R-J1-PDC Merkel Cell PMS2, PTEN 156681-154-R-J1-PDC Melanoma SF3B1 R196Q; BRAF V600E; ARID1A 168753-222-R-J1-PDC Bladder U2AF1 L5V; BRCA1; ATM; FGFR3; KIT 171881-019-R-J1-PDC Breast ATXN1, BRCA1, MUTYH, PIK3CA, MLH1, MSH3, ATXN2, TBX3, CDH1, TP53, BRIP1, KEAP1,PARP1 AMP; ATM, PALB2 186277-243-T-J2-PDC Colon BRCA2, KRAS G12D, PIK3CA, ATM, ARID1A, ARID4B, DNMT3A, TGFBR2, ATR, NF1 188146-221-R-J1-PDC Colon BRCA2, XRCC1, ATM, BRAF V600E; TGFBR2 217524-143-R1-J4-PDC Pancreas KRAS G12R; ARID1A; SMAD4; STK11 227483-062-R1-J1-PDC Pancreas KRAS G12V; ARID4B; SMAD4; MAP2K4 233499-124-R-J2-PDC Colon DYRK1B, KRAS A146T; ATR; MTOR; JAK1; APC 233499-124-R-J3-PDC Colon BRCA2, ATR, KRAS, MTOR, JAK1, APC, RAD50, KMT2C, CDKN1B, KMT2D, TP53 242566-281-R-J2-PDC Pancreas KRAS G12D, ARID1A 276233-004-R-J1-PDC Melanoma APC, KRAS G12S, RB1, ERBB4 282377-053-R-J1-PDC Colon POLQ, PARP1, ATR, APC, BRAF V600E; RAD50 292921-168-R-J2-PDC Pancreatic KRAS G12D, ARID1B, ARID1A, DNMT3A, APC, MET, FANCC, BRCA2, TP53, 299254-011-R-J1-PDC Melanoma CLK2, DYRK3, KRAS G12C, ARID1A, BRAF, APC, ATR, ATM, 317291-083-R-J1-PDC MPNST BRCA2, LATS1 323965-272-R-J2-PDC Pancreas KRAS G12C, ARID1A, FLT3 324938-238-R-PDC Bladder ERBB2, SMAD2, CREBBP, ERBB2, SMAD2, TP53 328373-195-R-J1-PDC Head and Neck CLK3, DYRK1B, RB1, RAD50 349418-098-R-PDC NSCLC BRAF V600E, ARID1A 377384-186-R-J1-PDC Pancreas KRAS G12D, ARID1A, RAD51B 379773-124-R-J2-PDC Endometrial ARID1A, FGFR2, PTEN 381356-305-R-J1-PDC Colon POLQ, MTOR, APC, TP53 422866-222-R5-J1-PDC Pancreas KRAS G12C, EGFR, SMAD3, BRCA1,TP53 435261-313-R-J1-PDC Colon APC, PIK3CA, KRAS G12V, RB1 439559-082-T-J2-PDC Colon BRCA1, BRCA2 AMP, APC, KRAS G12D 454973-116-R3-J5-PDC Pancreas DYRK1B, KRAS G12D, BRCA1, TP53 485176-168-R4-J1-PDC Pancreas TERT AMP, BRAF V600E, TGFBR2 485368-065-R4-J2-PDC Pancreas DYRK1B, KRAS G12V, ARID1A 496974-208-R-J2-PDC Pancreas U2AF1, spliceosome mutations, PTPRT 519858-162-T-J1-PDC Colon TERT, POLQ, APC, KRAS G12V, TP53 521955-158-R2-J5-PDC Pancreatic KRAS G12D, ATR, SMARCA4, ATR, TP53 556581-035-R-J1-PDC Ovarian ARID1B, ARID1A, PIK3CA 565232-114-T-J1-PDC Bladder APC, SMAD4, RUNX1 596521-263-R-J1-PDC MPNST TERT AMP 2; TP53 598228-144-R-J1-PDC Endometrial PIK3CA 598228-144-R-J1-PDC Endometrial PIK3CA, TP53 616215-338-R-J1-PDC Colon DYRK1A, DYRK1B, KRAS G12S, BRAF V600E, ARID1A, ATR 628569-122-R-J1-PDC Head and Neck SF3B1, ATM 633275-114-R-J1-PDC Endometrial PALB2 frameshift del, KRAS G12A, BRCA2, KEAP1 636577-100-R-J1-PDC Endometrial TERT, POLQ, TP53 648629-189-R-J1-PDC Bladder APC, PIK3CA, KLF2 653999-131-R-J2-PDC NSCLC BRCA1, BRCA2, KRAS G13D, TP53 695427-040-R-J1-PDC Colon BRCA2 AMP, APC, KRAS G12D, TP53 743489-274-T-PDC Renal Cell ARID1A, PIK3CA, BRCA1, PTEN, KMT2D, TP53 777334-354-R1-J3-PDC Pancreas POLR1A, BRCA2, KRAS G12D, TP53 786-0 Renal Cell ATM, ERCC3, HIF1A, KMT2D, MTOR, PDGFRA, PDGFRB, PTEN, SMAD2, TOP1, TP53, VHL 817829-284-R-J1-PDC Colon DYRK1A, DYRK1B, KRAS G12S, BRAF V600E, ARID1A, ATR 825966-067-R-J1-PDC Colon POLR1A, BRCA2, EGFR, BRAF V600E, TFGBR2, PIK3CA 855422-203-R-PDC Bladder PIK3CA, DICER1, TP53 857933-349-R-J2-PDC Colon BRCA2, PARP1, ATR, ATM, BRAF V600E, APC, TGFBR2 874868-142-R-J2-PDC Head and Neck DYRK2, DYRK4, FGFR3, SMAD4 876135-273-R-J2-PDC Melanoma CLK2, NRAS, NF1 876862-298-R-J1-PDC Endometrial CLK2, SF3B1, ARID1A, PIK3CA 883617-216-R-PDC Bladder EGFR, HRAS, KMT2C, ATM, KDM6A 885512-296-R-J2-PDC Breast TP53, STK11, KMT2C, KMT2D, RB1 885724-159-R-J1-PDC Pancreas BRCA1 AMP, KRAS G12V, TP53, ERBB2, SMAD4 922993-354-T-J2-PDC Endometrial ATM, BRCA2, TERT AMP, ATM, BRCA2 947758-054-R-J2-PDC Colon CLK3, DYRK1A, ARID1A, ATR, BRAF V600E 966289-007-R4-J1-PDC Pancreas BRAF, TP53 996289-038-R-J1-PDC Colon CLK4, DYRK3, KRAS G12D, APC 997537-175-T-J1-PDC Colon BRCA2, XRCC1, ATM, ATR, BRAF V600E A375 Melanoma BRAF V600G, CDKN2A, TERT A498 Renal Cell FGFR2, PDGFRA, POU2F2, PIK3CA, VHL IGROV1 Ovary BRCA1, BRCA2, PIK3CA, RB1, SMAD4, TP53 K24384-001-R-PDC Pancreas KRAS G12V, TP53, NOTCH1, ATM K-562 Leukemia BCR-ABL, ASXL1, HOXA9, NOTCH1, TP53 LG0703-F948-PDC NSCLC EGFR, TP53 MDA-MB-231 Breast, TNBC AR, ATM, BRAF, BRCA1, EGFR, KRAS, MYCL, NF1, NF2, NTRK1, PDGFRA, TMPRSS2, TP53 MDA-MB-468 Breast, TNBC ATR, BRCA2, BRD4, DDR2, FLT3, JAK1, KMT2C, NF1, NTRK3, PIK3CA, PTEN, TOP1, TP53 NCI/ADR-RES Ovary ARID1A, BRD4, CTNNB1, ERBB2, KMT2A, KRAS, RUNX1, TP53 NCI-H1876 SCLC (etop sensit) RB1, ARID1B, ERCC2, ERCC4, KDM6A, KMT2D, MYB, NOTCH2, NRAS, NTRK3, PDGFRA, PDGFRB, TP53 NCI-H196 SCLC (etop resist) RB1, BCL2, BRCA2, BRD3, BRD4, ERBB4, ERCC5, JAK2, KDM5A, MTOR, POLE, PTEN, SMAD2, TP53, USP6, WRN NCI-H211 SCLC (etop sensit) RB1wt, APOBEC3, FANCD2, MTOR, NOTCH2, PDGFRA, PIK3CA, POLQ, POU2AF1, SMARCA4, TP53 OVCAR-5 Ovary CREBBP, DICER1, ERCC2, EZH2, KRAS, NF1, NTRK3, TGFBR2 SUM149PT Breast, TNBC BRAF V600G, CDKN2A, TERT SW 1271 SCLC (etop resist) RB1, ABL1, ATM, BRAF, BRCA1, BRCA2, EGFR, ERCC2, FANCA, FGFR1, FGFR2, JAK2, JAK3, KDM5A, KEAP1, MYC, NF1, NRAS, PALB2, PIK3CB, PIK3R1, POU2AF1, TERT, TOP1, TP53, WRN Table 3 . Growth media and number of tumor cells, endothelial cells and human mesenchymal stem cells plated per well plated to form the mct-spheroids tested spheroids for response to cirtuvivint, CC-671 or iadademstat alone and in simultaneous combination with the compounds in Table 1 . The disease type and selected genetic properties for each line are shown. Cell lines are from the DCTD PDMR (https://pdmr.cancer.gov/). Malignant Cell Line Malignant Cell Growth Medium Malignant Cells per well HUVEC a per well hMSC b per well 138582-337-R-J1 Complete DMEM/F12 Media-Y 5000 2083 1250 156681-154-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 168753-222-R-J1 Complete DMEM/F12 Media-Y 5000 2083 1250 171881-019-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 186277-243-T-J2 Complete DMEM/F12 Media-Y 1250 521 313 188146-221-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 192522-019-R-J2 Complete DMEM/F12 Media-Y 5000 2083 1250 217524-143-R1-J4 Complete DMEM/F12 Media-Y 1250 521 313 227483-062-R1-J1 Panc + FBS 1250 521 313 233499-124-R-J2 Complete DMEM/F12 Media-Y 1250 521 313 233499-124-R-J3 Complete DMEM/F12 Media-Y 1250 521 313 242566-281-R-J2 Complete DMEM/F12 Media-Y 1250 521 313 276233-004-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 282377-053-R-J1 Complete DMEM/F12 Media-Y 625 260 156 292921-168-R-J2 Complete DMEM/F12 Media-Y 625 260 156 299254-011-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 317291-083-R-J1 Complete DMEM/F12 Media-Y 313 130 78 323965-272-R-J2 Complete DMEM/F12 Media-Y 1250 521 313 324938-238-R Complete DMEM/F12 Media-Y 1250 521 313 328373-195-R-J1 Complete DMEM/F12 Media-Y 625 260 156 349418-098-R Complete DMEM/F12 Media-Y 313 130 78 377384-186-R-J1 Complete DMEM/F12 Media-Y 313 130 78 379773-124-R-J2 Complete DMEM/F12 Media-Y 313 130 78 381356-305-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 422866-222-R5-J1 Complete DMEM/F12 Media-Y 1250 521 313 435261-313-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 439559-082-T-J2 Complete DMEM/F12 Media-Y 2500 1042 625 454973-116-R3-J5 Complete DMEM/F12 Media-Y 1250 521 313 485176-168-R4-J1 Panc + FBS 1250 521 313 485368-065-R4-J2 Complete DMEM/F12 Media-Y 2500 1042 625 496974-208-R-J2 Complete DMEM/F12 Media-Y 2500 1042 625 519858-162-T-J1 Complete DMEM/F12 Media-Y 2500 1042 625 521955-158-R2-J5 Complete DMEM/F12 Media-Y 1250 521 313 556581-035-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 565232-114-T-J1 Complete DMEM/F12 Media-Y 1250 521 313 596521-263-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 598228-144-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 616215-338-R-J1 Complete DMEM/F12 Media-Y 625 260 156 628569-122-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 633275-114-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 636577-100-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 648629-189-R-J1 Complete DMEM/F12 Media-Y 625 260 156 653999-131-R-J2 Complete DMEM/F12 Media-Y 1250 521 313 695427-040-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 743489-274-T Complete DMEM/F12 Media-Y 2500 1042 625 777334-354-R1-J3 Complete DMEM/F12 Media-Y 2500 1042 625 817829-284-R-J1 Complete DMEM/F12 Media-Y 625 260 156 825966-067-R-J1 Complete DMEM/F12 Media-Y 1250 521 313 855422-203-R-J1 Complete DMEM/F12 Media-Y 313 130 78 857933-349-R-J2 6C/COLON 1B -Y c 2500 1042 625 874868-142-R-J2 Complete DMEM/F12 Media-Y 2500 1042 625 876135-273-R-J2 Complete DMEM/F12 Media-Y 1250 521 313 876862-298-R-J1 6E + FBS + Y 2500 1042 625 883617-216-R-J1 Complete DMEM/F12 Media-Y 625 260 156 885512-296-R-J2 Complete DMEM/F12 Media-Y 313 130 78 885724-159-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 922993-354-T-J3 Complete DMEM/F12 Media-Y 2500 1042 625 947758-054-R-J2 6B/Colon 1A + FBS + Y 625 260 156 966289-007-R4-J1 Complete DMEM/F12 Media-Y 313 130 78 996289-038-R-J1 Complete DMEM/F12 Media-Y 2500 1042 625 997537-175-T-J1 Complete DMEM/F12 Media-Y 2500 1042 625 786-0 RPMI-1640 + 10% FBS 313 130 78 A375 HITES DMEM/F12 + 5% FBS 313 130 78 A498 RPMI-1640 + 10% FBS 1250 521 313 IGROV1 RPMI-1640/10% FBS/1% L-Glut 313 130 78 K24384-001-R-PDC Complete DMEM/F12 Media-Y 625 260 156 K562 RPMI-1640/10% FBS/1% L-Glut 313 130 78 LG0703-F948-PDC Complete DMEM/F12 Media-Y 625 260 156 MDA-MB-231 RPMI-1640/10% FBS/1% L-Glut 625 260 156 MDA-MB-468 RPMI-1640/10% FBS/1% L-Glut 625 260 156 NCI/ADR-RES RPMI-1640 + 10% FBS 313 130 78 NCI-H1876 HITES DMEM/F12 + 5% FBS 1250 521 313 NCI-H196 RPMI-1640 + 10% FBS 2500 1042 625 NCI-H211 RPMI-1640/10% FBS/1% L-Glut 313 130 78 OVCAR-5 RPMI-1640 + 10% FBS 1250 521 313 SUM149PT HAM’s F12 + 5% FBS 1250 521 313 SW 1271 HITES DMEM/F12 + 5% FBS 625 260 156 a human umbilical vein endothelial cells (HUVEC) b human mesenchymal stem cells (hMSC) c detailed descriptions of 6C/COLON 1B -Y and Breast #2 -Y are available at (https://pdmr.cancer.gov/). Table 4 . PubChem data files for the LSD1 screen and the CLK screen. File Name Group REGID AID Link to access data Anticancer human tumor 138582-337-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_01 1918931 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918931 Anticancer human tumor 171881-019-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_02 1918932 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918932 Anticancer human tumor 186277-243-T-J2-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_03 1918933 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918933 Anticancer human tumor 233499-124-R-J3-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_04 1918930 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918930 Anticancer human tumor 292921-168-R-J2-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_05 1918934 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918934 Anticancer human tumor 324938-238-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_06 1918935 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918935 Anticancer human tumor 349418-098-R-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_07 1918936 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918936 Anticancer human tumor 521955-158-R2-J5-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_08 1918937 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918937 Anticancer human tumor 556581-035-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_09 1918938 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918938 Anticancer human tumor 653999-131-R-J2-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_10 1918939 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918939 Anticancer human tumor 743489-274-T-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_11 1918942 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918942 Anticancer human tumor 786-0 cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_12 1918944 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918944 Anticancer human tumor 855422-203-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_13 1918943 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918943 Anticancer human tumor 883617-216-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_14 1918945 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918945 Anticancer human tumor 885512-296-R-J2-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_15 1918946 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918946 Anticancer human tumor A498 cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_16 1918947 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918947 Anticancer human tumor K24384-001-R-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_17 1918949 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918949 Anticancer human tumor K-562 cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_18 1918948 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918948 Anticancer human tumor K57222-313-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_19 1918950 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918950 Anticancer human tumor K60290-347-R-J1-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_20 1918951 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918951 Anticancer human tumor LG0703-F948-PDC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_21 1918952 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918952 Anticancer human tumor MDA-MB-231/ATCC cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_22 1918953 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918953 Anticancer human tumor MDA-MB-468 cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_23 1918954 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918954 Anticancer human tumor NCI/ADR-RES cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_24 1918955 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918955 Anticancer human tumor NCI-H1876 cell line growth inhibition [LSD1] Combinations_Synergy_Screen_LSD1 CSSLSD1_25 1918957 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918957 Anticancer human tumor NCI-H196 cell line growth inhibition [LSD1] Combinations_Synergy_Screen_LSD1 CSSLSD1_26 1918958 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918958 Anticancer human tumor NCI-H211 cell line growth inhibition [LSD1] Combinations_Synergy_Screen_LSD1 CSSLSD1_27 1918940 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918940 Anticancer human tumor OVCAR-5 cell line growth inhibition Combinations_Synergy_Screen_LSD1 CSSLSD1_28 1918956 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918956 Anticancer human tumor SW 1271 cell line growth inhibition [LSD1] Combinations_Synergy_Screen_LSD1 CSSLSD1_29 1918941 https://pubchem.ncbi.nlm.nih.gov/bioassay/1918941 Anticancer human tumor 156681-154-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_01 2060627 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060627 Anticancer human tumor 168753-222-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_02 2060626 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060626 Anticancer human tumor 186277-243-T-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_03 2060625 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060625 Anticancer human tumor 217524-143-R1-J4-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_04 2060624 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060624 Anticancer human tumor 227483-062-R1-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_05 2060623 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060623 Anticancer human tumor 233499-124-R-J3-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_06 2060613 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060613 Anticancer human tumor 242566-281-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_07 2060622 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060622 Anticancer human tumor 323965-272-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_08 2060619 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060619 Anticancer human tumor 324938-238-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_09 2060621 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060621 Anticancer human tumor 328373-195-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_10 2060620 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060620 Anticancer human tumor 377384-186-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_11 2060616 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060616 Anticancer human tumor 379773-124-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_12 2060604 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060604 Anticancer human tumor 422866-222-R5-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_13 2060603 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060603 Anticancer human tumor 454973-116-R2-J3-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_14 2060618 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060618 Anticancer human tumor 485368-065-R4-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_15 2060617 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060617 Anticancer human tumor 496974-208-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_16 2060615 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060615 Anticancer human tumor 565232-114-T-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_17 2060612 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060612 Anticancer human tumor 598228-144-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_18 2060614 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060614 Anticancer human tumor 616215-338-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_19 2060610 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060610 Anticancer human tumor 628569-122-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_20 2060611 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060611 Anticancer human tumor 648629-189-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_21 2060602 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060602 Anticancer human tumor 817829-284-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_22 2060599 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060599 Anticancer human tumor 855422-203-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_23 2060609 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060609 Anticancer human tumor 874868-142-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_24 2060601 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060601 Anticancer human tumor 876135-273-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_25 2060608 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060608 Anticancer human tumor 876862-298-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_26 2060607 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060607 Anticancer human tumor 922993-354-T-J3-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_27 2060606 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060606 Anticancer human tumor 947758-054-R-J2-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_28 2060605 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060605 Anticancer human tumor 996289-038-R-J1-PDC cell line growth inhibition [CLK] Combinations_Synergy_Screen_CLK CLK_29 2060600 https://pubchem.ncbi.nlm.nih.gov/bioassay/2060600 Additional Declarations No competing interests reported. Supplementary Files SupplyFig1.jpg Cite Share Download PDF Status: Published Journal Publication published 12 Sep, 2025 Read the published version in Cancer Chemotherapy and Pharmacology → Version 1 posted Editorial decision: Revision requested 12 Jul, 2025 Reviews received at journal 11 Jul, 2025 Reviewers agreed at journal 01 Jul, 2025 Reviewers invited by journal 09 May, 2025 Editor assigned by journal 06 May, 2025 Submission checks completed at journal 06 May, 2025 First submitted to journal 06 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6602839","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454108352,"identity":"628cdc8d-b26d-4a50-92ca-e621c76dc5d0","order_by":0,"name":"Beverly A. Teicher","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYBACezBZAGQcYGxgBjLlGJh58GsxbACRBgwMbAwQLcYEtRgcgGthYABpSWxgIGRLe4/h4wqDwwxs7M2Nnwsq7qVvZ+c9wPil4jBuv/CcMTY8A9LCc7BZesaZ4tydzXwJzDJncGsxnJGWJtkA0iKR2MbM25aQu+EwjwGzZFsabr/cf5b+E6xF/iFQy7+EdAOCWm4wH2OE2MII1NKQkADSwvixzQa3w3qSDwMdls7DxpPYLM1zLMEQ5LDDDGdwa7FnP9j4saHCWo6N/fjDzzw1CfIG588YPvxRIYFTCxQ0o8bFYQJRAwJ1qFzGH4S1jIJRMApGwcgBAAWzTpbN0RWOAAAAAElFTkSuQmCC","orcid":"","institution":"National Cancer Institute","correspondingAuthor":true,"prefix":"","firstName":"Beverly","middleName":"A.","lastName":"Teicher","suffix":""},{"id":454108353,"identity":"538392d3-a417-470f-bd68-5daae86734f2","order_by":1,"name":"Thomas S. Dexheimer","email":"","orcid":"","institution":"Frederick National Laboratory for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"S.","lastName":"Dexheimer","suffix":""},{"id":454108354,"identity":"f3cf5f7b-d778-45f4-a9e8-47abdd495993","order_by":2,"name":"Thomas Silvers","email":"","orcid":"","institution":"Frederick National Laboratory for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Silvers","suffix":""},{"id":454108355,"identity":"be732eaa-25d0-4a6d-95fb-855d70360f89","order_by":3,"name":"Nathan P. Coussens","email":"","orcid":"","institution":"Frederick National Laboratory for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Nathan","middleName":"P.","lastName":"Coussens","suffix":""},{"id":454108361,"identity":"05c0d9c5-63eb-4fed-9aa2-1b6a0bee3768","order_by":4,"name":"Eric Jones","email":"","orcid":"","institution":"Frederick National Laboratory for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"","lastName":"Jones","suffix":""},{"id":454108362,"identity":"57a385c1-4524-4d71-8139-e2b45668739b","order_by":5,"name":"Steven D. Gore","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Steven","middleName":"D.","lastName":"Gore","suffix":""},{"id":454108366,"identity":"847a626d-1ab5-4cb6-a743-6295f1a1a0c2","order_by":6,"name":"Mark Kunkel","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Kunkel","suffix":""},{"id":454108367,"identity":"e6c9438f-fe99-4078-8fed-d51892eb2b93","order_by":7,"name":"James H. Doroshow","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"H.","lastName":"Doroshow","suffix":""}],"badges":[],"createdAt":"2025-05-06 12:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6602839/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6602839/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00280-025-04800-w","type":"published","date":"2025-09-12T15:57:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82793225,"identity":"a2d6af74-25ce-4007-b857-8115e5ee45f9","added_by":"auto","created_at":"2025-05-15 10:24:17","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":201930,"visible":true,"origin":"","legend":"\u003cp\u003eSingle agent concentration response data for the pan-CLK inhibitor cirtuvivint, the CLK/TTK inhibitor CC-671and the KDM1A inhibitor idademstat in 26 human tumor cell lines \u0026nbsp;over a 9-point concentration range covering 4-logs of concentration after a 7-day exposure time. The chemical structures of cirtuvivint, CC-671, and iadademstat are shown.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/829c84a6904d7d302cedda98.jpg"},{"id":82793224,"identity":"eb2b2bcc-8b03-407d-8ca1-3d1693fecced","added_by":"auto","created_at":"2025-05-15 10:24:17","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":200149,"visible":true,"origin":"","legend":"\u003cp\u003eConcentration response data for the pan-CLK inhibitor cirtuvivint or the CLK/TTK inhibitor CC-671 tested in combination with the KRAS G12D selective inhibitor MRTX-1133. Data are shown for five PDMR human tumor cell lines grown as mct-spheroids, 186277-243-T-J2 TP53 wt, KRAS G12D colon carcinoma, 996289-038-R-J1 TP53 mutant, KRAS G12D, CLK4 mutant, DYRK3 mutant colon carcinoma, 377384-186-R-J1 TP53 mutant, KRAS G12D pancreatic carcinoma, 242566-281-R-J2 TP53 mutant, KRAS G12D pancreatic carcinoma and 616215-338-R-J1 TP53 wt, KRAS G12S, BRAF V600E. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/6f744bb431918c24f46298fe.jpg"},{"id":82795076,"identity":"8dbb082f-1a2d-4daf-aa5e-ec4e0ce32bca","added_by":"auto","created_at":"2025-05-15 10:32:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":222795,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the CLK/TTK inhibitor CC-671 tested in combination with the pan-PI3K inhibitor copanlisib. Data are shown for five PDMR human tumor cell lines grown as complex spheroids, 186277-243-T-J2 colon carcinoma, 168753-222-R-J1 bladder carcinoma, 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma. All data show the mean ± SD (n = 4). \u003cstrong\u003e3B\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the CLK/TTK inhibitor CC-671 tested in combination with the PI3Kalpha selective inhibitor inavolisib. Data are shown for five PDMR human tumor cell lines grown as mct-spheroids, 186277-243-T-J2 colon carcinoma, 168753-222-R-J1 bladder carcinoma, 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/4d15f17828af167caf2228f1.jpg"},{"id":82793230,"identity":"c692b2c7-0894-43d6-9795-302d37b6453b","added_by":"auto","created_at":"2025-05-15 10:24:17","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":195912,"visible":true,"origin":"","legend":"\u003cp\u003eConcentration response data for the pan-CLK inhibitor cirtuvivint or the CLK/TTK inhibitor CC-671 tested in combination with the XPO-1 inhibitor eltanexor. Data are shown for five PDMR human tumor cell lines grown as complex spheroids, 616215-338-R-J1 colon carcinoma, 996289-038-R-J1 colon carcinoma, 876135-273-R-J2 melanoma, 648629-189-R-J1 bladder carcinoma and 377384-186-R-J1-PDC pancreatic carcinoma. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/8d766c64eadf4d772ada7919.jpg"},{"id":82795081,"identity":"796c830a-8288-48e6-adb3-289df84b8409","added_by":"auto","created_at":"2025-05-15 10:32:17","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":195574,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the KDM1A/LSD1 inhibitor idademstat tested in combination with the DNA-PK inhibitor peposertib. Data are shown for five PDMR human tumor cell lines grown as mct-spheroids, 156681-154-R-J1 melanoma or186277-243-T-J2 colon carcinoma, 233499-124-R-J2 colon carcinoma, 324938-238-R bladder carcinoma, 616215-338-R-J1 colon carcinoma, and 565232-114-T-J1 bladder carcinoma. All data show the mean ± SD (n = 4). \u003cstrong\u003e5B\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the KDM1A inhibitor idademstat tested in combination with the topoisomerase 1 inhibitor SN-38. Data are shown for five PDMR human tumor cell lines grown as complex spheroids, 186277-243-T-J2 colon carcinoma, 233499-124-R-J2 colon carcinoma, 324938-238-R bladder carcinoma, 616215-338-R-J1 colon carcinoma, and 565232-114-T-J1 bladder carcinoma. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/a9facdf9fed92be0d8d729e5.jpg"},{"id":82795077,"identity":"a6687529-945d-4123-979b-742d00373eed","added_by":"auto","created_at":"2025-05-15 10:32:17","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":199040,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the KDM1A inhibitor idademstat tested in combination with the class I histone deacetylase (HDAC) inhibitor entinostat. Data are shown for five PDMR human tumor cell lines grown as mct-spheroids, 186277-243-T-J2 colon carcinoma, 233499-124-R-J2 colon carcinoma, 324938-238-R bladder carcinoma, 616215-338-R-J1 colon carcinoma, and 565232-114-T-J1 bladder carcinoma. All data show the mean ± SD (n = 4). \u003cstrong\u003e6B\u003c/strong\u003e. Concentration response data for the pan-CLK inhibitor cirtuvivint or the KDM1A inhibitor idademstat tested in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. Data are shown for five PDMR human tumor cell lines grown as complex spheroids, 186277-243-T-J2 colon carcinoma, 233499-124-R-J2 colon carcinoma, 324938-238-R bladder carcinoma, 616215-338-R-J1 colon carcinoma, and 565232-114-T-J1 bladder carcinoma. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/1241eb42fab134418fa32f02.jpg"},{"id":82793229,"identity":"6cd555e0-6071-48f7-93eb-00e078faea75","added_by":"auto","created_at":"2025-05-15 10:24:17","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":96437,"visible":true,"origin":"","legend":"\u003cp\u003eConcentration response data for the KDM1A inhibitor idademstat tested in combination with the NEDD8-activating enzyme (NAE) inhibitor pevonedistat or the ubiquitin activating enzyme (UAE) inhibitor TAK-243. Data are shown for the human K-562 leukemia which does not form spheroids, and four human solid tumor cell lines grown as mct-spheroids, 292921-168-R-J2 pancreatic carcinoma, 521955-158-R2-J5 pancreatic carcinoma, 556581-035-R-J1 ovarian carcinoma, and NCI/ADR-RES ovarian carcinoma. All data show the mean ± SD (n = 4).\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/408cb0160c85a82ffceff668.jpg"},{"id":91359173,"identity":"43f6234d-602e-4407-b276-9b17f31b9155","added_by":"auto","created_at":"2025-09-15 16:05:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2836976,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/04f32ce6-a1ea-4743-83e5-68bff4df2898.pdf"},{"id":82793222,"identity":"0a1ac96a-d86b-4e56-8e81-6ba6de4e4adc","added_by":"auto","created_at":"2025-05-15 10:24:16","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":48759,"visible":true,"origin":"","legend":"","description":"","filename":"SupplyFig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6602839/v1/ef9f3e93ec12796fa2c4f583.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe spliceosome, a critical intracellular organelle, is multi-megadalton complex composed of over 100 proteins including 5 small nuclear ribonucleoproteins. Cancer cells often have cancer type-specific RNA splicing alterations. Most multi-exon human genes undergo alternative splicing, allowing multiple mature mRNAs to be derived from a single gene [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Thus, 25,000 genes can code for well over 100,000 proteins. Pre-mRNA splicing, the process of removing introns from precursor messenger RNA, is critical in the post-transcriptional regulation of gene expression [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Serine/arginine (SR) family proteins control the patterns of alternative splicing in pre-mRNA and enhance splicing from nearby splice sites by interacting with exonic and intronic splicing enhancer sequences in pre-mRNA [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SR-proteins require phosphorylation by SR protein kinases (SRPKs), protein kinase B (PKB/AKT), NIMA-related kinase2 (NEK2), PRP4 kinase (PRP4K) dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), cAMP-dependent protein kinase (PKA) or by the CDC-like kinases (CLKs) to be active [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The CLKs regulate transcript RNA splicing through SR protein phosphorylation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Cirtuvivint is a pan CDC-like kinase (CLK1-4) and dual specificity tyrosine kinase (DYRK1-4) inhibitor which targets mRNA splicing and the Wnt pathway which is in clinical trial [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cirtuvivint exposure disrupts spliceosome activity and decreases production of Wnt signal pathway splicing variants. A Phase I clinical trial of cirtuvivint by oral administration, assessing dose escalation is currently active but not recruiting (NCT03355066) and the combination of cirtuvivint with ASTX727 in patients with acute myeloid leukemia or myelodysplastic syndromes is actively accruing patients (NCT06484062) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. CC-671, a CLK/TTK inhibitor has an inhibitory repertoire similar to cirtuvivint. TTK, also called Monopolar spindle 1 (Mps1), is a dual serine/threonine kinase that regulates the spindle assembly checkpoint, controlling cellular progression through mitosis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. CC-671 had in vivo activity in human tumor xenografts due to dual inhibition of CLK2/TTK [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLysine-specific demethylase 1α (LSD1) encoded by the KDM1A gene, is a lysine demethylase which has recurrent mutations, translocations, and somatic copy number gains or losses in human tumors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. LSD1/KDM1A removes mono- and dimethyl groups of histone H3 lysine-4 (H3K4), lysine-9 (H3K9) as well as non-histone substrates [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. LSD1 interacts with other chromatin regulators including histone deacetylases (HDAC)-1, 2 and 3, and DNA methyltransferase 1 (DNMT1). LSD1 is a component of a multi-subunit complex causing transcription activation or repression [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. LSD1 non-histone substrates are associated with the regulation of cell cycle progression and apoptosis. LSD1/KDM1A expression is associated with poor prognosis in prostate, breast, lung, bladder, colorectal cancer and neuroblastoma. Iadademstat is a potent LSD1 inhibitor with an IC\u003csub\u003e50\u003c/sub\u003e of 18 nM and \u0026gt;\u0026thinsp;1000-fold higher selectivity towards LSD1 compared to related FAD-dependent aminoxidases [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In AML models, LSD1 inhibition did not alter genome methylation but did increase me\u003csub\u003e2\u003c/sub\u003eH3K4 at LSD1 target genes [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In a small cell lung cancer xenograft, treatment with iadademstat resulted in NOTCH activation and ASCL1 suppression decreasing neuroendocrine properties [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWith the complexity of cancer genomic alterations, single targeted drugs are usually not sufficient to impact malignant disease, and combinations of targeted drugs are necessary for effective treatment. The current study was undertaken to explore the activity of RNA processing and epigenetic inhibitors in combination with other targeted agents and standard-of-care drugs in a mct-spheroid model from patient-derived tumor cell lines of the PDMR (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pdmr.cancer.gov/\u003c/span\u003e\u003cspan address=\"https://pdmr.cancer.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) or standard tumor cell lines and stromal cells. The full data sets are available at the PubChem files listed on Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003eompounds\u003c/strong\u003e.\u0026nbsp;The drugs and investigational agents: cirtuvivint (SM08502; NSC835563), CC-671 (NSC850746), iadademstat (NSC806812), vemurafenib (NSC761431), tapotoclax (NSC804041), sotorasib (NSC818433), adagrasib (NSC831453), MRTX-1133 (NSC836407), BAY2416964 (NSC825713), copanlisib (NSC816437), inavolisib (NSC800729), abemaciclib (NSC768073), osimertinib (NSC779217), entinostat (NSC756642), eltanexor (KPT-8602, NSC794443), venetoclax (NSC766270), ceralasertib (NSC777638), bortezomib (NSC756655), olaparib (NSC753686), talazoparib (NSC767125), adavosertib (NSC754677), alisertib (NSC759677), ART-558 (NSC835418), aza-T-dCyd (NSC777586), AZD-1390 (NSC803789), belinostat (NSC758774), camonsertib (NSC841442), CPI-455 (NSC825282), decitabine (NSC127716), elimusertib (NSC800525), \u0026nbsp;ixazomib (NSC758254), KSQ-4279 (NSC840948), panobinostat (NSC761190), peposertib (NSC802822), pevonedistat (NSC761192), R306465 (NSC773264), selinexor (NSC780203), TAK-243 (NSC785004), tazemetostat (NSC777109), topotecan (NSC609699), TP-3654 (NSC805149), eribulin (NSC707389), etoposide (NSC141540), carboplatin (NSC241240), cisplatin (NSC119875), gemcitabine (NSC613327), 5-fluorouracil (NSC19893), SN-38 (NSC673596), oxaliplatin (NSC266046), paclitaxel (NSC125973), and doxorubicin (NSC123127), were obtained from the National Cancer Institute (NCI) Developmental Therapeutics Program Chemical Repository [\u003cstrong\u003e20\u003c/strong\u003e]. The FDA-approved anticancer drug set is available from the Developmental Therapeutics Program at https://dtp.cancer.gov/organization/dscb/obtaining/available plates.htm. The drugs and investigational agents used were demonstrated to be \u0026gt;95% pure by proton nuclear magnetic resonance and liquid chromatography/mass spectrometry. The stock solutions were prepared in dimethyl sulfoxide (DMSO, Sigma-Aldrich, St. Louis, MO, cat. D2650), except for the platinum complexes which were prepared in saline (Quality Biological, Gaithersburg, MD, cat. 114-055-101), at 800-fold the tested concentration and stored at -70\u0026deg;C prior to their use. All drugs and investigational agents were tested over a range starting from a high concentration at or near the clinical C\u003csub\u003emax\u003c/sub\u003e and decreasing in half-log increments. If the clinical C\u003csub\u003emax\u003c/sub\u003e for an agent had not been determined, the highest concentration tested was 10 \u0026micro;M (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell Lines\u003c/strong\u003e. The patient-derived cancer (PDC) cell lines include 16 colon adenocarcinoma lines: \u0026nbsp; 186277-243-T-J2-PDC, 188146-221-R-J1-PDC, 282377-053-R-J1-PDC, 381356-305-R-J1-PDC, 435261-313-R-J1-PDC, 439559-082-T-J2-PDC, 519858-162-T-J1-PDC, \u0026nbsp;616215-338-R-J1-PDC, 695427-040-R-J1-PDC, 233499-124-R-J2-PDC, 817829-284-R-J1-PDC, 825966-067-R-J1-PDC, 857933-349-R-J2-PDC, 996289-038-R-J1-PDC, 997537-175-T-J1-PDC, and 947758-054-R-J2-PDC; 16 pancreatic carcinoma lines: 217524-143-R1-J4-PDC, 227483-062-R1-J1-PDC, 242566-281-R-J2-PDC, 292921-168-R-J2-PDC, 323965-272-R-J2-PDC, 377384-186-R-J1-PDC, 422866-222-R5-J1-PDC, 454973-116-R2-J3-PDC, 485176-168-R4-J1-PDC, 485368-065-R4-J2-PDC, 521955-158-R2-J5-PDC, 777334-354-R1-J3-PDC, 885724-159-R-J1-PDC, 966289-007-R4-J1-PDC, K24384-001-R-PDC, and 496974-208-R-J2-PDC; 6 bladder carcinoma lines: 168753-222-R-J1-PDC, 324938-238-R-J1-PDC, 565232-114-T-J1-PDC, 648629-189-R-J1-PDC, 883617-216-R-PDC, and 855422-203-R-J1-PDC; 7 endometrial carcinomas: 379773-124-R-J2-PDC, 598228-144-R-J1-PDC, 633275-114-R-J1-PDC, 636577-100-R-J1-PDC, 922993-354-T-J2-PDC, and 876862-298-R-J1-PDC; 3 head \u0026amp; neck squamous carcinoma: 328373-195-R-J1-PDC, 628569-122-R-J1-PDC, and 874868-142-R-J2-PDC; 4 melanoma: 156681-154-R-J1-PDC, 276233-004-R-J1-PDC, \u0026nbsp;299254-011-R-J1-PDC, and 876135-273-R-J2-PDC; 3 NSCLC: 349418-098-R-PDC, 653999-131-R-J2-PDC, and LG0703-F948-PDC; 2 \u0026nbsp;breast carcinoma: 171881-019-R-J1-PDC and 885512-296-R-J2-PDC; 2 MPNST: 317291-083-R-J1-PDC and 596521-263-R-J1-PDC; 1 ovarian carcinoma: 556581-035-R-J1-PDC; 1 renal cell carcinoma: 743489-274-T-PDC; and 1 Merkel cell tumor: 138582-337-R-J1-PDC, were obtained from the NCI Patient-Derived Models Repository (PDMR, https://pdmr.cancer.gov/) (\u003cstrong\u003eTable 2\u003c/strong\u003e). In addition, several standard human tumor cell lines were used including: 786-0 and\u0026nbsp;A498\u0026nbsp;renal cell carcinoma, \u0026nbsp;IGROV1,\u0026nbsp;NCI/ADR-RES\u0026nbsp;and\u0026nbsp;OVCAR-5 ovarian carcinoma; MDA-MB-231, MDA-MB-468, and SUM149PT TNBC; NCI-H1876, NCI-H196, NCI-H211 and SW 1271 SCLC; A375 melanoma and K562 leukemia were obtained from the NCI Tumor Repository (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u0026nbsp;Pooled donor human umbilical vein endothelial cells (HUVEC, Lonza, cat. CC-2519) and human mesenchymal stem cells (hMSC, Lonza, cat. PT-2501) were purchased from Lonza (Walkersville, MD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell Culture\u003c/strong\u003e. All cells were maintained in an incubator at 37\u0026deg;C and 5% CO\u003csub\u003e2\u003c/sub\u003e with 95% humidity. The PDC lines were cultured according to standard operating procedures established by the NCI PDMR (https://pdmr.cancer.gov). Briefly, all PDCs were thawed and cultured in Matrigel-coated flasks prepared with a working solution of 1X Ham\u0026apos;s F-12 nutrient mix, without supplementation (Invitrogen, Waltham, MA, cat. 11765054), 100 U/mL penicillin-streptomycin (Invitrogen, cat. 15140122), and 2.5% Matrigel (Corning Inc., Corning, NY, cat. 354248) for the first three passages. All PDCs were cultured in complete DMEM/F-12 media containing advanced DMEM/F-12 (Invitrogen, cat. 12634028), 4.9% defined fetal bovine serum, heat inactivated (HyClone Laboratories Inc., Logan, UT, cat. SH30070.03HI), 389 ng/mL hydrocortisone (Sigma-Aldrich, cat. H4001), 9.7 ng/mL human EGF recombinant protein (Invitrogen, cat. PHG0313), 23.4 \u0026micro;g/mL adenine (Sigma-Aldrich, cat. A2786), 97.3 U/mL penicillin-streptomycin (Invitrogen, cat. 15140122), 1.9 mM L-glutamine (Invitrogen, cat. 25030081), and 9.7 \u0026micro;M Y-27632 dihydrochloride (Tocris Bioscience, Bristol, United Kingdom, cat. 1254). The PDCs were cultured in complete DMEM/F12 media without 10 \u0026micro;M Y-27632 dihydrochloride for at least two passages prior to the screen, unless specified otherwise (\u003cstrong\u003eTable 3\u003c/strong\u003e). The established cell lines were cultured in RPMI-1640 medium, HEPES (Invitrogen, cat. 22400105) with 10% defined fetal bovine serum (HyClone Laboratories Inc., cat. SH30070.03) and 2 mM L-glutamine (Invitrogen, cat. 25030081), unless specified otherwise (\u003cstrong\u003eTable 3\u003c/strong\u003e). The pooled donor HUVEC and hMSC were cultured in endothelial cell growth medium 2 (PromoCell, Heidelberg, Germany, cat. C-22011) and mesenchymal stem cell growth medium 2 (PromoCell, cat. C-28009). For all experiments, HUVEC and hMSCs were used at passages \u0026le;5, while the malignant cell lines were used at passages \u0026le;15. Samples of the cell lines were collected at regular intervals throughout the screening process for short tandem repeat (STR) profiling and mycoplasma testing by Labcorp (Laboratory Corporation of America Holdings, Burlington, NC, formerly known as Genetica DNA Laboratories) to confirm their authenticity and integrity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHigh-throughput Drug Combination Screening.\u003c/strong\u003e Prior to their inoculation into microplates, malignant cells, HUVEC, and hMSC were removed from T flasks using TrypLE express (Invitrogen, cat. 12605036) and harvested by centrifugation for 5 min at 233 \u0026times; g. Following removal of the supernatant, the cells were resuspended in fresh medium and counted using a Cellometer auto T4 bright field cell counter (Nexcelom, Lawrence, MA) and trypan blue to distinguish viable cells. Multi-cell type (mct) tumor spheroids were grown from the mixture of three cell types: 60% malignant cells, 25% HUVECs, and 15% hMSCs as described previously 2]. Mixed cell suspensions of 50 \u0026micro;L were dispensed into the wells of 384-well black/clear round-bottom ULA spheroid microplates (Corning Inc., cat. 3830). Following inoculation, the microplates were transferred to an incubator (Thermo Fisher Scientific, Waltham, MA) and maintained at 37 \u0026deg;C and 5% CO\u003csub\u003e2\u003c/sub\u003e with 95% humidity. Three days after inoculation, test agents or controls were delivered to the wells of microplates. The approved and investigational anticancer agents, prepared as 800\u0026times; stock solutions, were subsequently transferred in 62.5 nL volumes to the appropriate wells of microplates using an I.DOT non-contact dispenser (DISPENDIX, Stuttgart, Germany) to achieve a 1x final concentration. All anticancer agents and their combinations were tested in quadruplicate. Additionally, each microplate included a DMSO vehicle control (\u003cem\u003en\u003c/em\u003e = 16) and a cytotoxicity control (1 \u0026micro;M staurosporine and 3 \u0026micro;M gemcitabine, \u003cem\u003en\u003c/em\u003e = 20). After delivery of the test agents and controls, the microplates were returned to the incubator for 7 days. Ten days after inoculation, the assay was completed with the addition of 20 \u0026micro;L CellTiter-Glo 3D (Promega, Madison, WI, cat. G9683) to each well. Next, the microplates were placed on a microplate shaker for 5 min. After 25 min of incubation at room temperature, luminescence was measured as a surrogate indicator of cell viability using a PHERAstar FSX microplate reader (BMG LABTECH, Cary, NC) [\u003cstrong\u003e21\u003c/strong\u003e, \u003cstrong\u003e22\u003c/strong\u003e].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Analysis\u003c/strong\u003e. Luminescence measurements from the screen were exported as comma separated values (CSV) files and imported into custom Excel spreadsheets (Microsoft, Redmond, WA) for analysis. The raw luminescence data were evaluated for quality control, filtered for outliers, and converted to percent viability by normalizing to the DMSO (vehicle-treated) control. Concentration-response data were fit to the four-parameter logistic equation using the Solver Add-In in Excel. The Bliss independence model states that if two drugs have independent activities, then the viability for the combination is equal to the product of the viability of the two single agents [\u003cstrong\u003e22\u003c/strong\u003e, \u003cstrong\u003e23\u003c/strong\u003e]. Synergy between two compounds was indicated by a lower observed percent viability than predicted by the Bliss independence model, whereas antagonism was indicated by a greater observed percent viability than predicted. The mean and statistical significance of Bliss independence scores for each drug combination-model across all concentrations and biological replicates were evaluated [\u003cstrong\u003e23\u003c/strong\u003e]. Response surface maps were generated using the MATLAB web application where blue indicates synergy and red indicates antagonism.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e. All data are accessible via the PubChem BioAssay public database (AID 1918931; AID1918932; AID1918933; AID1918930; AID1918934; AID1918935; AID1918936; AID1918937; AID1918938; AID8939; AID1918942; AID8944; AID1918943; AID1918945; AID1918946; AID1918947; AID1918949; AID1918948; AID8950; AID1918951; AID1918952; AID1918953; AID1918954; AID1918955; AID1918957; AID1918958; AID1918940; AID1918956; AID8941; AID2060627; AID 2060626; AID 2060625; AID 2060624; AID 2060623; AID 2060613; AID 2060622; AID 2060619; AID 2060621; AID 2060620; AID 2060616; AID 2060604; AID 2060603; AID 2060618; AID 2060617; AID 2060615; AID 2060612; AID 2060614; AID 2060610; AID 2060611; AID 2060602; AID 2060599; AID 2060609; AID 2060601; AID 2060608; AID 2060607; AID 2060606; AID 2060605; AID 2060600 (\u003cstrong\u003eTable 4\u003c/strong\u003e).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eSingle agent concentration response data for two investigational CLK inhibitors cirtuvivint and CC-671, and an investigational LSD1 inhibitor iadademstat, are shown in \u003cstrong\u003eFigure 1\u003c/strong\u003e. The compounds were tested 26 human tumor cells lines grown as mct-spheroids in 9-point concentration response at concentrations spanning 4-logs with an exposure time of 7 days. Cirtuvivint was the most potent cytotoxin with IC\u003csub\u003e90\u003c/sub\u003e concentrations between 0.2 to 10 µM. The LSD-1 inhibitor iadademstat was assessed in mct-spheroids in 29 cell lines including PDMR lines and established lines. The most responsive lines were the NCI-H211 SCLC, two triple-negative breast cancer lines MDA-MB-231 and MDA-MB-468, a pancreatic carcinoma line 292921-168-R-J2, and an ovarian carcinoma line 556581-035-R-J1; however, only the NCI-H211 mct-spheroids reached an IC\u003csub\u003e50\u003c/sub\u003e at 7.5 µM. Iadademstat was the least cytotoxic and reached an IC\u003csub\u003e50\u003c/sub\u003e concentration only in the MDA-MB-468 cell line at 10 µM, the highest concentration tested. Cirtuvivint, CC-671 and iadademstat were tested in combination with anticancer drugs and investigational agents in complex mct-spheroids composed of human tumor cells with known genetic alterations, HUVEC and hMSC cells. The drugs and investigational agents tested are listed in \u003cstrong\u003eTable 1\u003c/strong\u003e. The genetic variants for key genes in the tumor cell lines are shown on \u003cstrong\u003eTable 2\u003c/strong\u003e. Drugs and investigational agents were tested at concentrations beginning at the clinical Cmax concentration or at 10 µM, if the clinical Cmax \u0026nbsp;was not established, decreasing in half-log increments for 6 concentrations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe KRAS G12D selective inhibitor MRTX-1133 was assessed in combination with cirtuvivint in four PDMR lines harboring the KRAS G12D mutation and the 616215-338-R-J1 colon carcinoma which harbors a KRAS G12S mutation (\u003cstrong\u003eFigure 2\u003c/strong\u003e) [\u003cstrong\u003e24\u003c/strong\u003e]. The PDMR lines with KRAS G12D were among the most responsive to MRTX-1133 as a single agent with 377384-186-R-J1 pancreatic carcinoma mct-spheroids being most responsive. Simultaneous combination of cirtuvivint and MRTX-1133 produced primarily additive cytotoxicity with a few regions of great-than-additive cytotoxicity in the 186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma, 377384-186-R-J1 pancreatic carcinoma and 242566-281-R-J2 pancreatic carcinoma mct-spheroids with up to 2.5-3-logs of cell killing. The 616215-338-R-J1 colon carcinoma harboring a KRAS G12S mutation was also responsive to the combination of cirtuvivint and MTRX-1133. The response of the same five tumor mct-spheroids was assessed after 7-days exposure to CC-671 with MRTX-1133 (\u003cstrong\u003eFigure 2\u003c/strong\u003e). Tumor cell killing was greatest in the 377384-186-R-J1 pancreatic carcinoma complex mct-spheroids reaching 2-logs which was additive by the Bliss independence calculation. Greater-than-additive cell killing was evident under the same conditions for the 377384-186-R-J1 pancreatic carcinoma, the186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma mct-spheroids. The maximal tumor cell killing achieved with CC-671 and MRTX-1133 in the 377384-186-R-J1 pancreatic carcinoma, the 186277-243-T-J2 colon carcinoma, 996289-038-R-J1 colon carcinoma and 616215-338-R-J1 \u0026nbsp;colon carcinoma mct-spheroids was 1-log.\u003c/p\u003e\n\u003cp\u003eMoving down-stream of RAS, the simultaneous combination of cirtuvivint and the pan-PI3K inhibitor copanlisib was examined in five PDMR cell lines, the 186277-243-T-J2 colon carcinoma, the 168753-222-R-J1 bladder carcinoma, 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma mct-spheroids with a 7-day exposure (\u003cstrong\u003eFigure 3A\u003c/strong\u003e) [\u003cstrong\u003e25\u003c/strong\u003e]. The 168753-222-R-J1 bladder carcinoma mct-spheroids were more responsive to copanlisib as a single agent than were the 186277-243-T-J2 colon carcinoma mct-spheroids. The tumor cell killing was primarily additive in both tumor lines reaching 2-logs for the 186277-243-T-J2 colon carcinoma mct-spheroids and 3-logs for the168753-222-R-J1 bladder carcinoma mct-spheroids. The 947758-054-R-J2 colon carcinoma, 485368-065-R4-J2 pancreatic carcinoma and 454973-116-R3-J5 pancreatic carcinoma mct-spheroids with a 7-day exposure were similarly responsive to the combination of copanlisib and cirtuvivint with cell killing reaching 2- to -3-logs. The same five PDMR cell lines were exposed to CC-671 in simultaneous combination with copanlisib (\u003cstrong\u003eFigure 3A\u003c/strong\u003e). The combination of CC-671 with copanlisib was less cytotoxic than the combination of cirtuvivint with copanlisib in each of the five cell lines tested as mct-spheroids. The combination produced maximal cytotoxicity in the 168753-222-R-J1 bladder carcinoma mct-spheroids with additive to greater-than additive cell killing reaching 2-logs while the same combination produced less than 1-log of cell kiliing in the 485368-065-R4-J2 pancreatic carcinoma mct-spheroids. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe simultaneous combination of cituvivint and the PI3Ka\u0026nbsp;selective inhibitor inavolisib in\u0026nbsp;186277-243-T-J2 colon carcinoma\u0026nbsp;mct-spheroids resulted in additive to greater-than-additive cytotoxicity reaching a maximum to 2-logs (\u003cstrong\u003eFigure 3B\u003c/strong\u003e) [\u003cstrong\u003e26\u003c/strong\u003e]. As determined by the Bliss independence calculation the combination of cirtuvivint and inavolisib produced additive cell killing in the 168753-222-RJ1 bladder carcinoma mct-spheroids reaching 3-logs at the 2 highest concentrations of cirtuvivint across the concentration range of inavolisib. Greater-than-additive cell killing was seen with inavolisib in simultaneous combination with CC-671 in mct-spheroids grown from 947758-054-R-J2 colon carcinoma cells and 186277-243-T-J2 colon carcinoma cells (\u003cstrong\u003eFigure 3B\u003c/strong\u003e). Neither 947758-054-RJ2 colon carcinoma mct-spheroids nor 186277-243-TJ2 colon carcinoma mct-spheroids was very responsive to CC-671 reaching 62% and 70% cell killing, respectively. The combination of CC-671 and inavolisib reached nearly 2-logs of cell killing in both lines with more evidence of greater-than-additive cell killing occurring in the 947758-054-R-J2 colon carcinoma mct-spheroids. \u0026nbsp;Inavolisib was not effective in the 947758-054-R-J2 colon carcinoma mct-spheroids; however, greater-than-additive killing occurred over the 6x6 concentration matrix, the same was true of the combination of CC-671 and inavolisib in the 186277-243-TJ2 colon carcinoma mct-spheroids albeit the magnitude was less. Overall, the combination of CC-671 and inavolisib reached 1.5-logs of cell killing in both tumor lines.\u003c/p\u003e\n\u003cp\u003eAs a single agent the XPO1 inhibitor eltanexor, resulted in 1- to 2-logs of cytotoxicity in mct-spheroids after a 7-day exposure [\u003cstrong\u003e27\u003c/strong\u003e, \u003cstrong\u003e28\u003c/strong\u003e]. Five cell lines were selected to highlight the results from the combination of cirtuvivint and eltanexor (\u003cstrong\u003eFigure 4\u003c/strong\u003e). The simultaneous combination of cirtuvivint with eltanexor produced additive to greater-than-additive killing of 616215-338-R-J1 colon carcinoma mct-spheroids. While greater-than-additive cytotoxicity of the combination was observed at moderate concentrations of eltanexor and lower concentrations of cirtuvivint, cell killing of 2- to 3-logs was observed at the higher concentrations of both agents. The simultaneous combination of cirtuvivint and eltanexor produced greater-than-additive cytotoxicity at moderate concentrations of both agents in the 996289-038-R-J1 colon carcinoma mct-spheroids reaching 2.5-logs. The simultaneous combination of cirtuvivint and eltanexor was additive in the 876135-273-R-J2 melanoma, the 648629-189-R-J1 bladder carcinoma and 377384-186-R-J1 pancreatic carcinoma. Additive to less-than additive tumor cell killing occurred over a wide concentration range of both CC-671 and eltanexor in 616215-338-R-J1 colon carcinoma and the 996289-038-R-J1 colon carcinoma mct-spheroids reaching a maximum of about 1.5-logs. The greatest depth of tumor cell killing was observed in the 876135-273-R-J2 melanoma mct-spheroids reaching 3-logs at the two highest concentrations of CC-671 and eltanexor (\u003cstrong\u003eFigure 4\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe DNA-PK inhibitor peposertib was studied in combination with the CLK inhibitor cirtuvivint or with the LSD-1 inhibitor iadademstat (\u003cstrong\u003eFigure 5A\u003c/strong\u003e) [\u003cstrong\u003e29-31\u003c/strong\u003e]. While peposertib as a single agent was not highly effective in the five PDMR cell lines highlighted, 1566681-154-R-J1 melanoma, 233499-124-R-J3 and 616215-338-R-J1 colon carcinomas, 324938-238-R-1 and 565232-114-T-J1 bladder carcinomas, the combination of peposertib and cirtuvivint resulted in 2- to 3-logs of cell killing in each of the 5 lines grown as mct-spheroids. In contrast, the combination of peposertib with the LSD-1 inhibitor iadademstat resulted in sub-additive to additive cell killing in the five PDMR lines highlighted, 186277-243-T-J2 and 233499-124-R-J3 colon carcinomas, 324938-238-R-1 bladder carcinoma, 743899-274-T renal cell carcinoma and 521955-158-R2-J5 pancreatic carcinoma (\u003cstrong\u003eFigure 5A\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSN-38 is the active metabolite of the prodrug irinotecan, that acts, like irinotecan, by inhibiting topoisomerase I, an enzyme induces a single strand break in DNA to relax the DNA during replication [\u003cstrong\u003e32, 33\u003c/strong\u003e]. SN-38 was tested at concentrations up to 1µM during the 7-day exposure period (\u003cstrong\u003eFigure 5B\u003c/strong\u003e). At the lower concentrations of cirtuvivint and moderate to high concentrations of SN-38 marked greater-than-additive tumor cell killing with Bliss additivity scores up to 66 for the 616215-338-R-J1 colon carcinoma, 58 for the 233499-124-R-J3 colon carcinoma, 40 for the 565232-114-T-J1 bladder carcinoma, and 21 for the 186277-243-T-J2 colon carcinoma while, the combination of cirtuvivint and SN-38 produced additive cytotoxicity due to the sensitivity of the 186277-243-T-J2 mct-spheroid to SN-38 which killed 1-log of cells as a single agent (\u003cstrong\u003eFigure 5B\u003c/strong\u003e). By comparison, the combination of iadademstat and SN-38 produced less-than-additive to additive cell killing over the iadademstat \u0026nbsp;and SN-38 concentrations tested.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe histone deacetylase inhibitor entinostat was tested in combination with cirtuvivint and iadademstat and the results from five PDMR human tumor cell lines grown as mct-spheroids are shown in \u003cstrong\u003eFigure 6A\u0026nbsp;\u003c/strong\u003e[\u003cstrong\u003e34, 35\u003c/strong\u003e]. The combination of entinostat with cirtuvivint were additive in the five cell lines highlighted over the concentration ranges of the drugs tested with a 7-day exposure time. A similar result was obtained with the combination of iadademstat with entinostat with the five PDMR cells lines grown as mct-spheroids producing less-than-additive to additive cytotoxicity.\u003c/p\u003e\n\u003cp\u003eCombinations of cirtuvivint and iadadematat with the PARP1 inhibitor olaparib in five of the PDMR tumor cell lines grown as mct-spheroids resulted in the combination producing sub-additive to additive cytotoxic effects in the 324938-238-R-1 and 565232-114-T-J1 bladder carcinomas and additive to greater-than additive cytotoxicity in the 186277-243-T-J2 and 616215-338-R-J1 colon carcinomas (\u003cstrong\u003eFigure 6B\u003c/strong\u003e)[\u003cstrong\u003e36\u003c/strong\u003e]. The combination of iadademstat with olaparib resulted in little cytotoxicity with combinations just reaching an IC\u003csub\u003e50\u003c/sub\u003e with the highest concentration of both drugs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIadademstat was tested with the NEDD8-activating enzyme (NAE) inhibitor pevonedistat (\u003cstrong\u003eFigure 7\u003c/strong\u003e). Pevonedistat prevents the activation of cullin-RING E3 ligases thereby blocking the ubiquitination and proteasomal degradation of cellular proteins causing a build-up of proteins leading to cell death [\u003cstrong\u003e37-41\u003c/strong\u003e]. The K-562 leukemia was responsive to pevonedistat reaching 1 log of cytotoxicity at the highest concentration (3\u0026nbsp;mM) tested. There was an iadademstat concentration dependent increase in cytotoxicity with iadademstat and pevonedistat reaching 2-logs at 3\u0026nbsp;mM pevonedistat (\u003cstrong\u003eFigure 7\u003c/strong\u003e). Of the two PDMR pancreatic carcinoma lines, the less responsive the 521955-158-R2-J5 pancreatic carcinoma mct-spheroids reached \u0026gt;1-log, while the 292921-186-R-J2 pancreatic carcinoma mct-spheroids reached 2-logs of cell killing at higher pevonedistat concentrations. The OVCAR-5, and NCI/ADR-RES ovarian carcinoma mct- spheroids were responsive to pevonedistat reaching 1-log at 3mM pevonedistat. Combination of pevonedistat with iadademstat did not increase OVCAR-5 or NCI/ADR-RES mct-spheroid killing compared with pevonedistat alone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTAK-243 is an inhibitor of the (UAE). UAE is the primary E1 enzyme regulating the ubiquitin conjugation cascade [\u003cstrong\u003e42-43\u003c/strong\u003e]. The binding of TAK-243 to UAE prevents protein ubiquitination resulting in protein accumulation (proteotoxic stress) and leading to cell death. The K-562 leukemia was responsive to TAK-243 with 3-logs of cytotoxicity at the highest concentration of TAK-243 (0.3\u0026nbsp;mM) tested (\u003cstrong\u003eFigure 7\u003c/strong\u003e). Iadademstat with TAK-243 resulted in an iadademstat concentration dependent increase in K-562 leukemia cell cytotoxicity at the lower concentrations of TAK-243 compared with TAK-243 alone. Two of the PDMR pancreatic carcinoma, 292921-186-R-J2 and 521955-158-R2-J5, were as responsive to TAK-243 as was the K-562 leukemia reaching 3-logs of cytotoxicity. Iadademstat with TAK-243 increase in cytotoxicity in the two pancreatic carcinoma mct-spheroids compared with TAK-243. TAK-243 and iadademstat produced a modest increase in cytotoxicity. The PDMR 556581-035-R-J1 ovarian carcinoma was highly responsive to TAK-243 reaching 3-logs of cytotoxicity. Iadademstat with TAK-243 increased cytotoxicity compared with TAK-243 alone at the mid-range concentrations. The NCI/ADR-RES ovarian carcinoma mct-spheroids were responsive to TAK-243 reaching 2-logs of cytotoxicity. Iadademstat with TAK-243 was less cytotoxic than TAK-243 as a single agent in the NCI/ADR-RES cell line. The OVCAR-5 cell line was responsive to TAK-243 reaching nearly 2-logs of cell killing. The combination of iadademstat and TAK-243 was modestly more cytotoxic than TAK-243.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMost genes with multiple introns and exons undergo alternative splicing to generate multiple mRNAs which are then translated into the diversity of proteins making up cellular proteins required for differentiation, development, and cell death in a process performed by \u0026nbsp;spliceosomes, highly complex structures made up of approximately 300 proteins and RNA [\u003cstrong\u003e45-47\u003c/strong\u003e]. The Cancer Genome Atlas (TCGA) indicates that many solid tumors and hematologic malignancies deregulate DYRK1A. The pan-CLK/DYRK inhibitor cirtuvivint can cause programmed cell death at concentrations which inhibit the accumulation of phosphorylated SR proteins and alter splicing decreasing cellular proliferation in hematologic PDXs [\u003cstrong\u003e45\u003c/strong\u003e]. Cirtuvivint inhibits spliceosome associated CLK kinases especially SRSF5/6, thus, providing indirect inhibition of Wnt signaling resulting in antitumor activity [\u003cstrong\u003e46\u003c/strong\u003e]. Approximately 90% of colorectal cancers have\u0026nbsp;mutations in the Wnt/β-catenin signaling pathway and aberrant Wnt signaling often occurs in gastric, pancreatic, breast and other cancers [\u003cstrong\u003e46\u003c/strong\u003e]. CC-671 is a potent and selective inhibitor of both TTK (human protein kinase monopolar spindle 1 [hMps1]) and CDC like kinase 2 (CLK2). A protein docking analysis indicated that \u0026nbsp;CC-671 has high binding affinity to the drug-binding site of ABCG2 [\u003cstrong\u003e47\u003c/strong\u003e]. While dysregulation and alteration in pre-mRNA splicing is a recognized therapeutic target in hematologic malignancies, targeting pre-mRNA splicing has only been pursued recently for solid tumors. Pre-mRNA splicing modulation followed by PARP inhibition or chemotherapy in BRCA-mutant breast and ovarian cancers characterized by a “BRCA-ness” phenotype of dysfunctional homologous DNA repair [\u003cstrong\u003e48\u003c/strong\u003e].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpliceosome-associated SR protein kinases SRPKs, CLKs, and NEK2 are altered in many cancers [\u003cstrong\u003e49\u003c/strong\u003e]. The CLK kinase family which includes CLK1-4, in conjunction with SRPK kinases adjust phosphorylation of SR proteins to modulate alternative splicing. CLK kinase activity changes are associated with cancer development and progression. Phosphorylation of SR proteins impact their subcellular localization, association with the spliceosome complex, and splicing activity[\u003cstrong\u003e49\u003c/strong\u003e].SRSF5 and SRSF3 were reported to be overexpressed in oral squamous cell carcinoma (OSCC), and necessary for OSCC cell proliferation, cell cycle progression, and in vivo tumor formation. SRSF5-7 were found to be upregulated in small cell lung cancer (SCLC) and NSCLC tissues, and knockdown of SRSF5-7 in SCLC cell lines showed a significant decrease in proliferation [\u003cstrong\u003e49\u003c/strong\u003e].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEpigenetic mechanisms control gene expression patterns without change in DNA sequence. Histones, DNA binding proteins involved in regulation of nucleosome function, are subject to methylation, acetylation, phosphorylation, and ubiquitination. The methylation and demethylation of lysine residues on histone tails are post-translational protein modifications which control gene expression. The KDM (K=lysine) demethylase gene family includes 20 KDMs. KDM1s utilize a flavin adenine dinucleotide cofactor to demethylate methylated lysine substrates. KDM1A regulates many aspects of cell biology including self-renewal, differentiation, and stem cell pluripotency [\u003cstrong\u003e50\u003c/strong\u003e]. The protein encoded by the KDM1A gene is LSD1 which removes mono- and dimethyl groups from histone H34K and other chromatin-associated proteins. \u0026nbsp;Two ways epigenetic therapies act as anticancer therapies are repression of oncogene function or activation of tumor-suppressor genes [\u003cstrong\u003e51\u003c/strong\u003e]. LSD1 is overexpressed in many proliferative diseases including hematological, lung, breast, and prostate cancers.\u0026nbsp;Iadademstat, an irreversible LSD1 inhibitor, is in clinical development\u0026nbsp;[\u003cstrong\u003e52-54\u003c/strong\u003e]. Several LSD1 inhibitors have completed Phase 1 clinical trial and have moved on to Phase 2 studies [\u003cstrong\u003e55\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;56\u003c/strong\u003e]. Pevonedistat interferes with the function of the proteasome pathway blocking NAE. The PDMR 292921-168-R-J2 pancreatic carcinoma mct-spheroids was most responsive to pevonedistat reaching 2-logs of cytotoxicity and the K-562 leukemia, the PDMR 521955-158-R-J5 pancreatic carcinoma and the ovarian carcinoma lines OVCAR-5 and NCI/ADR-RES mct-spheroids reached 1-log of cytotoxicity upon exposure to pevonedistat for 7 days. The combination of iadademstat and pevonedistat resulted in increased cytotoxicity in the K-562 leukemia and the PDMR 556581-035-R-J1 ovarian carcinoma compared with single agent pevonedistat (\u003cstrong\u003eFigure 7\u003c/strong\u003e). TAK-243 was markedly cytotoxic as a single agent in the K-562 leukemia, in 2 of 3 PDMR pancreatic carcinomas, 292921-168-R-J2 and 521955-158-R-J5, and the PDMR 556581-035-R-J1 ovarian carcinoma resulting in 3-logs of cytotoxicity at the highest concentration (0.3\u0026nbsp;mM) tested. There was little increase in response with iadademstat and TAK-243.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA first-in-human phase 1 iadademstat clinical study was conducted in relapsed refractory acute leukemia enriched with MLL/KMT2A-rearranged acute myeloid leukemia patients with most having MLL-translocation disease. The pharmacokinetic data indicate that the iadademstat clinical Cmax concentration was 0.116-0.182 nM, a concentration below the concentration range of 0.1-10 µM in the current study [\u003cstrong\u003e57\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;58\u003c/strong\u003e]. Some patients with a molecular response to treatment with iadademstat showed blast cell differentiation, but no clinical responses were seen. In the current screen of 29 cell lines and 25 drugs and investigational agents indicate that response is highly cell line dependent. Although genetic marker(s) that might correlate with response to the combination regimens were sought no clear marker(s) emerged.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261201500003I.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBAT, NPC and TSD wrote the main manuscript text and BAT and TS prepared figures 1-7. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data are available in PubChem as shown in the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBradley RK, Anczuk\u0026oacute;w O. RNA splicing dysregulation and the hallmarks of cancer. Nature Rev Cancer 2023; 23: 135\u0026ndash;55.\u003c/li\u003e\n\u003cli\u003eAubol BE, Wozniak JM, Fattet L, Gonzalez DJ, Adams JA. CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly. Proc Natl Acad Sci 2021; 118: e2018251118.\u003c/li\u003e\n\u003cli\u003eYoshimi A, Abdel-Wahab O. Molecular pathways: understanding and targeting mutant spliceosomal proteins. Clin Cancer Res 2017; 23: 336-41.\u003c/li\u003e\n\u003cli\u003eMoyano PM, Nemec V, Paruch K. Cdc-like kinases (CLKs): biology, chemical probes, and therapeutic potential. Int J Mol Sci 2020; 21: 7549.\u003c/li\u003e\n\u003cli\u003eSong M, Pang L, Zhang M, Qu Y, Laster KV, Dong Z. Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases. Sig Transduc Targ Therap 2023; 8:148.\u003c/li\u003e\n\u003cli\u003eCorr BR, Moroney MR, Woodruff E, Watson ZL, Jordan KR, Danhorn T, Bailey C, Wolsky RJ, Bitler BG. Combination CDC-like kinase inhibition (CLK)/Dual-specificity tyrosine-regulated kinase (DYRK) and taxane therapy in \u003cem\u003eCTNNB1\u003c/em\u003e-mutated endometrial cancer. bioRxiv: posted April 6, 2023.\u003c/li\u003e\n\u003cli\u003eRiggs JR, Nagy M, Elsner J, Erdman P, Cashion D, Robinson D, Harris R, Huang D, Tehrani L, Deyanat-Yazdi G, Narla RK, Peng X, Tran T, Barnes L, Miller T, Katz J, Tang Y, Chen M, Moghaddam MF, Bahmanyar S, Pagarigan B, Delker S, LeBrun L, Chamberlain PP, Calabrese A, Canan SS, Leftheris K, Zhu D, Boylan JF. The discovery of a dual TTK protein kinase/CDC2-like kinase (CLK2) inhibitor for the treatment of triple negative breast cancer initiated from a phenotypic screen. J Med Chem 2017; 60: 8989-9002.\u003c/li\u003e\n\u003cli\u003eZhu D, Xu S, Deyanat-Yazdi G, Peng SX, Barnes LA, Narla RK, Tran T, Mikolon D, Ning Y, Shi T, Jiang N, Raymon HK, Riggs JR, Boylan JF. Synthetic lethal strategy identifies a potent and selective TTK and CLK1/2 inhibitor for treatment of triple-negative breast cancer with a compromised G1\u0026ndash;S checkpoint. Mol Cancer Ther 2018; 1: 17: 27\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eMcGrath J, Trojer P. Targeting histone lysine methylation in cancer. Pharmacol Ther 2015; 150: 1-22.\u003c/li\u003e\n\u003cli\u003eSchmidt DMZ, McCafferty DG. Trans-2-phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochem 2007; 46: 4408-16.\u003c/li\u003e\n\u003cli\u003eShi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA\u003cem\u003e, \u003c/em\u003eet al\u003cem\u003e. \u003c/em\u003eHistone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell\u003cem\u003e \u003c/em\u003e2004; 119: 941-53.\u003c/li\u003e\n\u003cli\u003eMcGrath JP, Williamson KE, Balasubramanian S, Odate S, Arora S, Hatton C, Edwards TM, Thomas O\u0026apos;Brien T, Magnuson S, Stokoe D, Daniels DL, Bryant BM, Patrick Trojer P. Pharmacological inhibition of the histone lysine demethylase KDM1A suppresses the growth of multiple acute myeloid leukemia subtypes. Cancer Res 2016; 76: 1975-88.\u003c/li\u003e\n\u003cli\u003eWang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine GG, et al\u003cem\u003e. \u003c/em\u003eOpposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 2007; 446: 882-7.\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e \u003c/em\u003eMaes T, Carceller E, Salas J, Ortega A, Buesaet C. Advances in the development of histone lysine demethylase inhibitors. Curr Opin Pharmacol 2015; 23: 52-60.\u003c/li\u003e\n\u003cli\u003eHarris WJ\u003cem\u003e,\u003c/em\u003eHuang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y, Ciceri F, Blaser JG, Greystoke BF, Jordan AM, Miller CJ, Donald J. Ogilvie DJ, Somervaille TCP. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 2012; 21: 473\u0026ndash;87.\u003c/li\u003e\n\u003cli\u003eSchenk T, Chen WC, G\u0026ouml;llner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, Casero RA, Marton L, Woster P, Minden MD, Dugas M, Wang JCY, Dick JE, M\u0026uuml;ller-Tidow C, Petrie K, Zelent A. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nature Med 2012; 18: 605-11.\u003c/li\u003e\n\u003cli\u003eMaes T, Tirapu I, Mascar\u0026oacute; C, Ortega A, Estiarte A, Castro-Palomino NV, Arjol CB, Guido Kurzet G. Preclinical characterization of a potent and selective inhibitor of the histone demethylase KDM1A for MLL leukemia. J Clin Oncol 2013; 31: e13543.\u003c/li\u003e\n\u003cli\u003eSmitheman K, Cusan M, Liu Y, Butticello M, Pappalardi M, Foley J, Federowicz K, Van Aller G, Kasparec J, Tian X, Suarez D, Schneck J, Carson J, McDevitt P, Ho T, McHugh C, Miller W, Armstrong S, Hann C, Johnson N, Kruger RG, Mohammad HP, Shekhar Kamat S. Inhibition of LSD1 for the treatment of cancer. Cancer Res 2015; 75: 3513. \u003c/li\u003e\n\u003cli\u003eAugert A, Eastwood E, Ibrahim AH, Wu N, Grunblatt E, Basom R\u003cem\u003e, \u003c/em\u003eet al\u003cem\u003e. \u003c/em\u003eTargeting NOTCH activation in small cell lung cancer through LSD1 inhibition. Sci Signal\u003cem\u003e \u003c/em\u003e2019; 12: 10.1126/scisignal.aau2922. \u003c/li\u003e\n\u003cli\u003eMorris J, Kunkel MW, White SL, Wishka DG, Lopez OD, Bowles L, et al. Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems-based Resource. Mol Cancer Ther 2023;22:1270-9.\u003c/li\u003e\n\u003cli\u003eKaur G, Evans DM, Teicher BA, Coussens NP. Complex Tumor Spheroids, a Tissue-Mimicking Tumor Model, for Drug Discovery and Precision Medicine. SLAS Discov \u003cstrong\u003e2021\u003c/strong\u003e;26:1298-314.\u003c/li\u003e\n\u003cli\u003eDexheimer TS, Coussens NP, Silvers T, Wright J, Morris J, Doroshow JH, Teicher BA. Multicellular complex tumor spheroid response to DNA repair inhibitors in combination with DNA-damaging drugs. Cancer Res Commun 2023; 3(8): 1648-61.\u003c/li\u003e\n\u003cli\u003eBliss CI. The Toxicity of Poisons Applied Jointly. Annals of Applied Biology 1939;26:585-615.\u003c/li\u003e\n\u003cli\u003eWang XL, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, et al.\u003cem\u003e \u003c/em\u003eIdentification of MRTX1133, a Noncovalent, Potent, and Selective KRAS Inhibitor. J Med Chem 2022; 65: 3123-33.\u003c/li\u003e\n\u003cli\u003eSkanland SS, Okkenhaug K, Davids MS. PI3K inhibitors in hematology: when one door closes. Clin Cancer Res 2024; 30: 3667\u0026ndash;75.\u003c/li\u003e\n\u003cli\u003eSong KW, Edgar KA, Hanan EJ, Hafner M, Oeh J, Merchant M, Sampath D, Nannini MA, Hong R, Phu L, Forrest WF, Stawiski E, Schmidt S, Endres N, Guan J, Wallin JJ, Cheong J, Plise EG, Lewis Phillips GD, Salphati L, Heffron TP, Alan G. Olivero AG, Malek S, Staben ST,Kirkpatrick DS, Dey A, Friedman LS. RTK-dependent inducible degradation of mutant PI3Ka drives GDC-0077 (inavolisib) efficacy. Cancer Discov 2022;12: 204\u0026ndash;19.\u003c/li\u003e\n\u003cli\u003eCamilli S, Lockey R, Kolliputi N. Nuclear export inhibitors selinexor (KPT-330) and eltanexor (KPT-8602) provide a novel therapy to reduce tumor growth by induction of PANoptosis. Cell Biochem Biophys 2023; 81: 421\u0026ndash;26.\u003c/li\u003e\n\u003cli\u003eBinder AF, Walker CJ, Mark TM, Baljevic M Impacting T-cell fitness in multiple myeloma: potential roles for selinexor and XPO1 inhibitors. Front Immunol 2023; 14: 1275329.\u003c/li\u003e\n\u003cli\u003eGordhandas SB, Manning-Geist B, Henson C, Iyer G, Gardner GJ, Sonoda Y, Moore KN, Aghajanian C, Chui MH, Grisham RN. Preclinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer. Scientific Reports 2022; 12: 974. \u003c/li\u003e\n\u003cli\u003evan Bussel MTJ, Awada A, de Jonge MJA, Mau-S\u0026oslash;rensen M, Nielsen D, Sch\u0026ouml;ffski P, Verheul HMW, Sarholz B, Berghoff K, El Bawab S, Kuipers M, Damstrup L, Diaz-Padilla I, Schellens JHM. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumors. Brit J Cancer 2021; 124: 728\u0026ndash;35. \u003c/li\u003e\n\u003cli\u003eSamuels M, Falkenius J, Bar-Ad V, Dunst J, Triest B, Yachnin J, Rodriguez-Gutierrez A, Kuipers M, You X, Sarholz B, Locatelli G, Becker A, Troost EGC. A Phase1studyof the DNA-PK inhibitor peposertib in combination with radiation therapy with or without cisplatin in patients with advanced head and neck tumors. Int J Radiat Oncol Biol Phys 2024; 118: 743-56.\u003c/li\u003e\n\u003cli\u003eJandu H, Aluzaite K, Fogh L, Thrane SW, Noer JB, Proszek J, Do KN, Hansen SN, Damsgaard B, Nielsen SL, Stougaard M, Knudsen BR, Moreira J, Hamerlik P, Gajjar M, Smid M, Martens J, Foekens J, Pommier Y, Br\u0026uuml;nner N, Schrohl AS, Stenvang J. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. BMC Cancer 2016;16:34.\u003c/li\u003e\n\u003cli\u003eJensen NF, Agama K, Roy A, Smith DH, Pfister TD, R\u0026oslash;mer MU, Zhang HL, Doroshow JH, Knudsen BR, Stenvang J, Br\u0026uuml;nner N, Pommier Y. Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations. J Exp Clin Cancer Res 2016;35:56. \u003c/li\u003e\n\u003cli\u003eLian B, Chen X, Shen K. Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer. Front Immunol 2023;14:1164514. \u003c/li\u003e\n\u003cli\u003eWang C, Lin Y, Zhu H, Zhou Y, Mao F, Huang X, Sun Q, Li C. Efficacy and Safety Profile of Histone Deacetylase Inhibitors for Metastatic Breast Cancer: A Meta-Analysis. Front Oncol. 2022;12:901152.\u003c/li\u003e\n\u003cli\u003eAwasthi S, Dobrolecki LE, Sallas C, Zhang X, Li Y, Khazaei S, Ghosh S, Jeter CR, Liu J, Mills GB, Westin SN, Lewis MT, Peng W, Sood AK, Yap TA, Yi SS, McGrail DJ, Sahni N. UBA1 inhibition sensitizes cancer cells to PARP inhibitors. Cell Rep Med. 2024; 5:101834.\u003c/li\u003e\n\u003cli\u003eSoucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature\u003cem\u003e \u003c/em\u003e2009; 458: 732\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eSoucy TA, Smith PG, Rolfe M. Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer. Clin Cancer Res\u003cem\u003e \u003c/em\u003e2009; 15: 3912\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eSwords RT, Kelly KR, Smith PG, et al. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood\u003cem\u003e \u003c/em\u003e2010; 115: 3796\u0026ndash;800. \u003c/li\u003e\n\u003cli\u003eFerris J, Espona-Fiedler M, Hamilton C, Holohan C, Crawford N, McIntyre AJ, Roberts JZ, Wappett M, McDade SS, Daniel B. Longley DB, Coyle V. Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer. Cell Death Discov 2020, 6:61. \u003c/li\u003e\n\u003cli\u003eHyer ML, Milhollen MA, Ciavarri J, Fleming P, Traore T, Sappal D, Huck J, Shi J, Gavin J, Brownell J, Yang Y, Stringer B, Griffin R, Bruzzese F, Soucy T, Duffy J, Rabino C, Riceberg J, Hoar K, Lublinsky A, Menon S, Sintchak M, Bump N, Pulukuri SM, Langston S, Tirrell S, Kuranda M, Veiby P, Newcomb J, Li P, Wu JT, Powe J, Dick LR, Greenspan P, Galvin K, Manfredi M, Claiborne C, Amidon BS, Bence NF. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat Med 2018; 24: 186-93. \u003c/li\u003e\n\u003cli\u003eArakawa Y, Jo U, Kumar S, Sun NY, Elloumi F, Thomas A, Roper N, Varghese DG, Takebe N, Zhang X, Ceribelli M, Holland DO, Beck E, Itkin Z, McKnight C, Wilson KM, Travers J, Klumpp-Thomas C, Thomas CJ, Hoang CD, Hernandez JM, Del Rivero J, Pommier Y. Activity of the ubiquitin-activating enzyme Inhibitor TAK-243 in adrenocortical carcinoma cell lines, patient-derived organoids, and murine xenografts. Cancer Res Commun 2024; 4:834-48.\u003c/li\u003e\n\u003cli\u003eWu Z, Yang Y, Lei Z, Narayanan S, Wang J, Teng Q, Murakami M, Ambudkar SV, Ping F, Chen Z. ABCB1 limits the cytotoxic activity of TAK-243, an inhibitor of the ubiquitin-activating enzyme UBA. Front Biosci (Landmark Ed). 2022; 27:5. \u003c/li\u003e\n\u003cli\u003eBonner EA, Lee SC. Therapeutic targeting of RNA splicing in cancer. Genes 2023; 14: 1378. \u003c/li\u003e\n\u003cli\u003eTam BY, Chiu K, Chung H, Bossard C, Nguyen JD, Creger E, Eastman BW, Mak CC, Ibanez M, Ghias A, Cahiwat J, Do L, Cho S, Nguyen J, Deshmukh V, Stewart J, Chen CW, Barroga C, Dellamary L, KC SK, Phalen TJ, Hood J, Cha S, Yusuf Yazici Y. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Letters 2020; 473: 186-97.\u003c/li\u003e\n\u003cli\u003eWu ZX, Yang Y, Wang G, Wang JQ, Teng QX, Sun L, Lei ZN, Lin L, Chen ZS, Zou C.\u003cem\u003e \u003c/em\u003eDual TTK/CLK2 inhibitor, CC-671, selectively antagonizes ABCG2-mediated multidrug resistance in lung cancer cells. Cancer Sci\u003cem\u003e \u003c/em\u003e2020; 111: 2872\u0026ndash;82.\u003c/li\u003e\n\u003cli\u003eWheeler EC, Martin BJE, Doyle WC, Neaher S, Conway CA, Pitton CN, Gorelov RA, Donahue M, Jann JC, Abdel-Wahab O, Taylor J, Seiler M, Buonamici S, Pikman Y, Garcia JS, Belizaire R, Adelman K, Tothova Z. Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML. Sci Transl Med 2024; 16: eade2774.\u003c/li\u003e\n\u003cli\u003eMurphy AJ, Li AH, Li P, Sun H. Therapeutic targeting of alternative splicing: A new frontier in cancer treatment. Front Oncol 2022; 12: 868664.\u003c/li\u003e\n\u003cli\u003eKurmasheva RT, Erickson SW, Han R, Teicher BA, Smith MA, Roth M, Gorlick R, Houghton PJ. In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). Pediatr Blood Cancer 2021; 68: e29304.\u003c/li\u003e\n\u003cli\u003eTremblay D, Mesa R. Novel treatments for myelofibrosis: beyond JAK inhibitors. Int J Hematol 2022; 115: 645-58.\u003c/li\u003e\n\u003cli\u003eSacilotto N, Dessanti P, Lufino MMP, Ortega A, Rodr\u0026iacute;guez-Gimeno A, Salas J, Maes T, Buesa C, Mascar\u0026oacute; C, Soliva R. Comprehensive in vitro characterization of the LSD1 small molecule inhibitor class in oncology. ACS Pharmacol Transl Sci 2021; 4: 1818\u0026minus;34.\u003c/li\u003e\n\u003cli\u003eSoldi S, Halder TG, Weston A, Thode T, Drenner K, Lewis R, Kaadige MR, Srivastava S, Ampanattu SD, del Villar RR, Lang J, Vankayalapati H, Weissman B, Trent JM, Hendricks WPD, Sharma S.The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-Non-Fermentable (SWI/SNF) complex mutated ovarian cancer. PLoS ONE 2020; 15: e0235705.\u003c/li\u003e\n\u003cli\u003eHodges S, Cooney J. Novel lysine-specific histone demethylase 1 inhibitor in acute myeloid leukemia transformed from essential thrombocythaemia. Cancer Rep 2022; 5: e1588.\u003c/li\u003e\n\u003cli\u003eFang Y, Liao G, Bin Yu B. LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol 2019; 12:129 .\u003c/li\u003e\n\u003cli\u003eClement Agboyibor C, Dong J, Effah CY, Drokow EK, Pervaiz W, Liu HM. LSD1 as a biomarker and the outcome of its inhibitors in the clinical trial: the therapy opportunity in tumors. J Oncol 2021: .5512524\u003c/li\u003e\n\u003cli\u003eHiatt JB, Sandborg H, Garrison SM, Arnold HU, Liao SY, Norton JP, Friesen TJ, Wu F, Sutherland KD, Rienhoff Jr. HY, Martins R, Houghton AM, Srivastava S, MacPherson D. Inhibition of LSD1 with bomedemstat sensitizes small cell lung cancer to immune checkpoint blockade and T cell killing. Clin Cancer Res 2022; 28: 4551-64.\u003c/li\u003e\n\u003cli\u003eSalamero O, Montesinos P, Willekens C, P\u0026eacute;rez-Sim\u0026oacute;n JA, Pigneux A, R\u0026eacute;cher C, Popat R, Carpio C, Molinero C, Mascar\u0026oacute; C, Vila J, Ar\u0026eacute;valo MI, Maes T, Buesa A, Bosch F, Somervaille TCP. First-in-human Phase I study of iadademstat (ORY-1001): a first-in-class lysine-specific histone demethylase 1A inhibitor, in relapsed or refractory acute myeloid leukemia. J Clin Oncol 2020; 38: 4260\u0026ndash;73.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Drugs and investigational agents for pidnarulex (CX-5461), APTO-253(LOR-253), BRACO-19, iadademstat, cirtuvivint and CC-671 combination mct-spheroid screens.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"634\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrug or Invest Ag\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNSC #\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClin Cmax\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(10 uM default)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTarget\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCirtuvivint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e835563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e427.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e3 \u0026micro;M\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eCLKs/DYRKs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCC-671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e805746\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e512.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eCLK2/TTK\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eIadademestat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e806812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e230.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLSD1 (KDM1A)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e5-Fluorouracil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e19893\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e130.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e426 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eThymidylate synthase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAbemaciclib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e763073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.59 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eCDK4/6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAdagrasib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e831453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e604.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e3 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eKRAS G12C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAdavosertib (MK-1775)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e754352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e500.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eWEE-1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAlisertib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e759677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAurora Kinase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eART-558\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e835418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e418.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePOLQ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAza-T-dCyd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e777586\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e244.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.3 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDNMT1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eAZD-1390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e803789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e477.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eATM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eBAY2416964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e825713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e378.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAhR inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eBelinostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e758774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e134 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eBortezomib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e756655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.312 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eProteasome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCamonsertib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e841442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e410.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eATR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCarboplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e241240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e371.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e135 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDNA crosslinking\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCeralasertib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e780249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e412.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eATR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e119875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e14.4 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCopanlisib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e816437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e480.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.964 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAKT \u0026alpha;/\u0026delta;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eCPI-455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e825282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e314.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eKDM5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eDacitabine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e127716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.323 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDNMT1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eDoxorubicin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e123127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.73 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTopII/DNA intercalator\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eElimusertib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e800525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e375.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eATR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eEltanexor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e794443\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e428.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eXPO1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eEntinostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e756642\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e376.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eEribulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e707389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.508 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTubulin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eEtoposide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e141540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e588.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e33.4 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTopII inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eGemcitabine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e613327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e89.3 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAntimetabolite/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eInavolisib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e800729\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e407.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePIK3CA,\u0026nbsp;PI3Ka\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eIxazomib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e758254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e517\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.118 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eProteasome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eKSQ-4279 (R07623066)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e840948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e534.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eUSP1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eMRTX-1133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e836407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e600.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eKRAS G12D\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eOlaparib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e753686\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e13.1 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePARP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eOsimertinib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e779217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.126 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eEGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eOxaliplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e266046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e397\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e4.96 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eDNA crosslinker\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003ePaclitaxel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e125973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e854\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e4.27 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTubulin stabilizer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003ePanobinostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e761190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.082 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003ePeposertib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e802822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e481.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDNA-PK\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003ePevonedistat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e761192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e443.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNAE (NEDD8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eR306465\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e773264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e413.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eSelinexor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e780203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e443.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.53 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCRM1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eSN-38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e673596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e392.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTopI inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eSotorasib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e818433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eKRAS G12C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTAK-243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e785004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e519.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.3 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eUAE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTalazoparib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e767125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e380.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.043 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePARP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTapotoclax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e804041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e613.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMCL-1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTazemetostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e777109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e572.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1.45 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eEZH2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTopotecan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e609699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.015 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTopI inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eTP-3654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e805149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e418.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e10 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePIM-1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eVemurafenib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e761431\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e127 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBRAF V600E\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003eVenetoclax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e766270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e4.48 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 192px;\"\u003e\n \u003cp\u003eBCL-2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Tumor cell lines tested as complex spheroids (including endothelial cells and mesenchymal stem cells) for response to cirtuvivint, CC-671 or iadademstat alone and in simultaneous combination with the compounds in \u003cstrong\u003eTable 1\u003c/strong\u003e. The disease type and key genetic aberrations for each line are shown. Some lines are from the DCTD PDMR (https://pdmr.cancer.gov/).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"587\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCell Line\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKey Mutations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e138582-337-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMerkel Cell\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePMS2, PTEN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e156681-154-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMelanoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eSF3B1 R196Q; BRAF V600E; ARID1A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e168753-222-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eU2AF1 L5V; BRCA1; ATM; FGFR3; KIT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e171881-019-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBreast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eATXN1, BRCA1, MUTYH, PIK3CA, MLH1, MSH3, ATXN2, TBX3, CDH1, TP53, BRIP1, KEAP1,PARP1 AMP; ATM, PALB2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e186277-243-T-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, KRAS G12D, PIK3CA, ATM, ARID1A, ARID4B, DNMT3A, TGFBR2, ATR, NF1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e188146-221-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, XRCC1, ATM, BRAF V600E; TGFBR2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e217524-143-R1-J4-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12R; ARID1A; SMAD4; STK11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e227483-062-R1-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12V; ARID4B; SMAD4; MAP2K4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e233499-124-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK1B, KRAS A146T; ATR; MTOR; JAK1; APC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e233499-124-R-J3-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, ATR, KRAS, MTOR, JAK1, APC, RAD50, KMT2C, CDKN1B, KMT2D, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e242566-281-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12D, ARID1A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e276233-004-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMelanoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eAPC, KRAS G12S, RB1, ERBB4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e282377-053-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePOLQ, PARP1, ATR, APC, BRAF V600E; RAD50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e292921-168-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreatic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12D, ARID1B, ARID1A, DNMT3A, APC, MET, FANCC, BRCA2, TP53,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e299254-011-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMelanoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK2, DYRK3, KRAS G12C, ARID1A, BRAF, APC, ATR, ATM,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e317291-083-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMPNST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, LATS1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e323965-272-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12C, ARID1A, FLT3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e324938-238-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eERBB2, SMAD2, CREBBP,\u0026nbsp;ERBB2, SMAD2, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e328373-195-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHead and Neck\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK3, DYRK1B, RB1, RAD50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e349418-098-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNSCLC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRAF V600E, ARID1A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e377384-186-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12D, ARID1A, RAD51B\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e379773-124-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eARID1A, FGFR2, PTEN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e381356-305-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePOLQ, MTOR, APC, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e422866-222-R5-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12C, EGFR, SMAD3, BRCA1,TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e435261-313-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eAPC, PIK3CA, KRAS G12V, RB1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e439559-082-T-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA1, BRCA2 AMP, APC, KRAS G12D\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e454973-116-R3-J5-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK1B, KRAS G12D,\u0026nbsp;BRCA1, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e485176-168-R4-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eTERT AMP, BRAF V600E, TGFBR2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e485368-065-R4-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK1B, KRAS G12V, ARID1A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e496974-208-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eU2AF1, spliceosome mutations, PTPRT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e519858-162-T-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eTERT, POLQ, APC, KRAS G12V, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e521955-158-R2-J5-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreatic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12D, ATR, SMARCA4, ATR, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e556581-035-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eOvarian\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eARID1B, ARID1A, PIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e565232-114-T-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eAPC, SMAD4, RUNX1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e596521-263-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMPNST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eTERT AMP 2; TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e598228-144-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e598228-144-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePIK3CA, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e616215-338-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK1A, DYRK1B, KRAS G12S, BRAF V600E, ARID1A, \u0026nbsp;ATR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e628569-122-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHead and Neck\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eSF3B1, ATM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e633275-114-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePALB2 frameshift del, KRAS G12A, BRCA2, KEAP1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e636577-100-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eTERT, POLQ, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e648629-189-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eAPC, PIK3CA, KLF2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e653999-131-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNSCLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA1, BRCA2, KRAS G13D, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e695427-040-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2 AMP, APC, KRAS G12D, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e743489-274-T-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRenal Cell\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eARID1A, PIK3CA, BRCA1, PTEN, KMT2D, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e777334-354-R1-J3-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePOLR1A, BRCA2, KRAS G12D, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e786-0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRenal Cell\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eATM, ERCC3, HIF1A, KMT2D, MTOR, PDGFRA, PDGFRB, PTEN, SMAD2, TOP1, TP53, VHL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e817829-284-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK1A, DYRK1B, KRAS G12S, BRAF V600E, ARID1A, ATR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e825966-067-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePOLR1A, BRCA2, EGFR, BRAF V600E, TFGBR2, PIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e855422-203-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003ePIK3CA,\u0026nbsp;DICER1, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e857933-349-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, PARP1, ATR, ATM, BRAF V600E, APC, TGFBR2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e874868-142-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHead and Neck\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eDYRK2, DYRK4, FGFR3, SMAD4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e876135-273-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMelanoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK2, NRAS, NF1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e876862-298-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK2, SF3B1, ARID1A, PIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e883617-216-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBladder\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eEGFR, HRAS, KMT2C, ATM, KDM6A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e885512-296-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBreast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eTP53, STK11, KMT2C, KMT2D, RB1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e885724-159-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA1 AMP, KRAS G12V, TP53, ERBB2, SMAD4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e922993-354-T-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eATM, BRCA2,\u0026nbsp;TERT AMP, ATM, BRCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e947758-054-R-J2-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK3, DYRK1A, ARID1A, ATR, BRAF V600E\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e966289-007-R4-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRAF, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e996289-038-R-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCLK4, DYRK3, KRAS G12D, APC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e997537-175-T-J1-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eColon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA2, XRCC1, ATM, ATR, BRAF V600E\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eA375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMelanoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRAF V600G, CDKN2A, TERT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eA498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eRenal Cell\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eFGFR2, PDGFRA, POU2F2, PIK3CA, VHL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eIGROV1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eOvary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRCA1, BRCA2, PIK3CA, RB1, SMAD4, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eK24384-001-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eKRAS G12V, TP53, NOTCH1, ATM\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eK-562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eLeukemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBCR-ABL, ASXL1, HOXA9, NOTCH1, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eLG0703-F948-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eNSCLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eEGFR, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eMDA-MB-231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBreast, TNBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eAR, ATM, BRAF, BRCA1, EGFR, KRAS, MYCL, NF1, NF2, NTRK1, PDGFRA, TMPRSS2, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eMDA-MB-468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBreast, TNBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eATR, BRCA2, BRD4, DDR2, FLT3, JAK1, KMT2C, NF1, NTRK3, PIK3CA, PTEN, TOP1, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eNCI/ADR-RES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eOvary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eARID1A, BRD4, CTNNB1, ERBB2, KMT2A, KRAS, RUNX1, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eNCI-H1876\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSCLC (etop sensit)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eRB1, ARID1B, ERCC2, ERCC4, KDM6A, KMT2D, MYB, NOTCH2, NRAS, NTRK3, PDGFRA, PDGFRB, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eNCI-H196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSCLC (etop resist)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eRB1, BCL2, BRCA2, BRD3, BRD4, ERBB4, ERCC5, JAK2, KDM5A, MTOR, POLE, PTEN, SMAD2, TP53, USP6, WRN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eNCI-H211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSCLC (etop sensit)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eRB1wt, APOBEC3, FANCD2, MTOR, NOTCH2, PDGFRA, PIK3CA, POLQ, POU2AF1, SMARCA4, TP53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eOVCAR-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eOvary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eCREBBP, DICER1, ERCC2, EZH2, KRAS, NF1, NTRK3, TGFBR2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eSUM149PT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eBreast, TNBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eBRAF V600G, CDKN2A, TERT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eSW 1271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eSCLC (etop resist)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 401px;\"\u003e\n \u003cp\u003eRB1, ABL1, ATM, BRAF, BRCA1, BRCA2, EGFR, ERCC2, FANCA, FGFR1, FGFR2, JAK2, JAK3, KDM5A, KEAP1, MYC, NF1, NRAS, PALB2, PIK3CB, PIK3R1, POU2AF1, TERT, TOP1, TP53, WRN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Growth media and number of tumor cells, endothelial cells and human mesenchymal stem cells plated per well plated to form the mct-spheroids tested spheroids for response to cirtuvivint, CC-671 or iadademstat alone and in simultaneous combination with the compounds in \u003cstrong\u003eTable 1\u003c/strong\u003e. The disease type and selected genetic properties for each line are shown. Cell lines are from the DCTD PDMR (https://pdmr.cancer.gov/).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignant Cell Line\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignant Cell\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGrowth Medium\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignant Cells\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eper well\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHUVEC\u003csup\u003ea\u003c/sup\u003e \u003cbr\u003e\u0026nbsp;per well\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ehMSC\u003csup\u003eb\u003c/sup\u003e \u003cbr\u003e\u0026nbsp;per well\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e138582-337-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e156681-154-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e168753-222-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e171881-019-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e186277-243-T-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e188146-221-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e192522-019-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e217524-143-R1-J4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e227483-062-R1-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePanc + FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e233499-124-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e233499-124-R-J3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e242566-281-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e276233-004-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e282377-053-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e292921-168-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e299254-011-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e317291-083-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e323965-272-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e324938-238-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e328373-195-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e349418-098-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e377384-186-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e379773-124-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e381356-305-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e422866-222-R5-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e435261-313-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e439559-082-T-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e454973-116-R3-J5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e485176-168-R4-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePanc + FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e485368-065-R4-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e496974-208-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e519858-162-T-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e521955-158-R2-J5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e556581-035-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e565232-114-T-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e596521-263-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e598228-144-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e616215-338-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e628569-122-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e633275-114-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e636577-100-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e648629-189-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e653999-131-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e695427-040-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e743489-274-T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e777334-354-R1-J3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e817829-284-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e825966-067-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e855422-203-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e857933-349-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6C/COLON 1B -Y\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e874868-142-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e876135-273-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e876862-298-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6E + FBS + Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e883617-216-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e885512-296-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e885724-159-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e922993-354-T-J3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e947758-054-R-J2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6B/Colon 1A + FBS + Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e966289-007-R4-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e996289-038-R-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e997537-175-T-J1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e786-0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640 + 10% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eA375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHITES DMEM/F12 + 5% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eA498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640 + 10% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eIGROV1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640/10% FBS/1% L-Glut\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eK24384-001-R-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eK562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640/10% FBS/1% L-Glut\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLG0703-F948-PDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete DMEM/F12 Media-Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMDA-MB-231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640/10% FBS/1% L-Glut\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMDA-MB-468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640/10% FBS/1% L-Glut\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCI/ADR-RES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640 + 10% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCI-H1876\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHITES DMEM/F12 + 5% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCI-H196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640 + 10% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCI-H211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640/10% FBS/1% L-Glut\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOVCAR-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRPMI-1640 + 10% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSUM149PT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHAM\u0026rsquo;s F12 + 5% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSW 1271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHITES DMEM/F12 + 5% FBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003ehuman umbilical vein endothelial cells (HUVEC)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e human mesenchymal stem cells (hMSC)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003ec\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003edetailed descriptions\u0026nbsp;of\u0026nbsp;6C/COLON 1B -Y and\u0026nbsp;Breast #2 -Y\u003csup\u003e\u0026nbsp;\u003c/sup\u003eare available at (https://pdmr.cancer.gov/).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e. PubChem data files for the LSD1 screen and the CLK screen.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFile Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eREGID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLink to access data\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 138582-337-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918931\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 171881-019-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918932\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918932\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 186277-243-T-J2-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918933\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918933\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 233499-124-R-J3-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918930\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918930\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 292921-168-R-J2-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918934\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918934\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 324938-238-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918935\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 349418-098-R-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918936\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 521955-158-R2-J5-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918937\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918937\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 556581-035-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918938\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918938\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 653999-131-R-J2-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918939\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918939\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 743489-274-T-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918942\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 786-0 cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918944\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918944\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 855422-203-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918943\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918943\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 883617-216-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918945\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 885512-296-R-J2-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918946\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918946\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor A498 cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918947\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor K24384-001-R-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918949\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918949\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor K-562 cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918948\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor K57222-313-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918950\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor K60290-347-R-J1-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918951\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor LG0703-F948-PDC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918952\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918952\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor MDA-MB-231/ATCC cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918953\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918953\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor MDA-MB-468 cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918954\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor NCI/ADR-RES cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918955\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor NCI-H1876 cell line growth inhibition [LSD1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918957\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor NCI-H196 cell line growth inhibition [LSD1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918958\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor NCI-H211 cell line growth inhibition [LSD1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor OVCAR-5 cell line growth inhibition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918956\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918956\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor SW 1271 cell line growth inhibition [LSD1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_LSD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCSSLSD1_29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1918941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/1918941\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 156681-154-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060627\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 168753-222-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060626\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060626\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 186277-243-T-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 217524-143-R1-J4-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 227483-062-R1-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060623\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 233499-124-R-J3-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060613\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 242566-281-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060622\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 323965-272-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060619\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 324938-238-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060621\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 328373-195-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060620\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 377384-186-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060616\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 379773-124-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060604\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 422866-222-R5-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060603\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060603\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 454973-116-R2-J3-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060618\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 485368-065-R4-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060617\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 496974-208-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060615\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060615\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 565232-114-T-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060612\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 598228-144-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060614\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060614\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 616215-338-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060610\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 628569-122-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 648629-189-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060602\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 817829-284-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060599\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 855422-203-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060609\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 874868-142-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060601\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060601\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 876135-273-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060608\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 876862-298-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060607\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060607\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 922993-354-T-J3-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060606\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060606\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 947758-054-R-J2-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060605\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060605\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003eAnticancer human tumor 996289-038-R-J1-PDC cell line growth inhibition [CLK]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCombinations_Synergy_Screen_CLK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCLK_29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2060600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ehttps://pubchem.ncbi.nlm.nih.gov/bioassay/2060600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cancer-chemotherapy-and-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccap","sideBox":"Learn more about [Cancer Chemotherapy and Pharmacology](http://link.springer.com/journal/280)","snPcode":"280","submissionUrl":"https://submission.nature.com/new-submission/280/3","title":"Cancer Chemotherapy and Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6602839/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6602839/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe alternative splicing of mRNA precursors allows one gene to yield multiple proteins with distinct functions. CDC-like kinases (CLKs) serve as pivotal regulators of alternative splicing. Control of protein expression also occurs at the level of DNA through histone methylation and demethylation. We investigated the activity of two CLK inhibitors, cirtuvivint and CC-671, and the LSD1 inhibitor iadademstat alone and in combination with anticancer drugs or investigational agents. Well-characterized patient-derived cancer cell lines from the PDMR (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pdmr.cancer.gov/models/database.htm\u003c/span\u003e\u003cspan address=\"https://pdmr.cancer.gov/models/database.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) were used along with standard human cancer cell lines. Multi-cell type (mct) tumor spheroids were grown from a ratio of 6:2.5:1.5 malignant cells, endothelial cells, and mesenchymal stem cells. Following three days of growth, the spheroids were exposed to the single agents or combinations at concentrations up to the clinical C\u003csub\u003emax\u003c/sub\u003e value for each agent, if known. After seven days of exposure, cell viability was assessed using the CellTiter-Glo 3D assay and spheroid volume was assessed by bright field imaging. Several of the targeted oncology drugs exhibited additive and greater-than-additive cytotoxicity when combined with a CLK inhibitor, or the LSD1 inhibitor. These agents included the XPO1 inhibitor, eltanexor, and the KRAS G12D specific inhibitor MRTX-1133 which had activity in tumor lines harboring the KRAS G12D mutation. LSD1 inhibition was effective with ubiquitin proteasome pathway inhibitors. The full data sets are available on PubChem.\u003c/p\u003e","manuscriptTitle":"RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 10:24:12","doi":"10.21203/rs.3.rs-6602839/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-12T05:30:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-11T14:49:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106367988571030679871712459431742659242","date":"2025-07-01T14:10:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-09T05:45:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-06T15:10:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-06T15:06:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cancer Chemotherapy and Pharmacology","date":"2025-05-06T12:00:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cancer-chemotherapy-and-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccap","sideBox":"Learn more about [Cancer Chemotherapy and Pharmacology](http://link.springer.com/journal/280)","snPcode":"280","submissionUrl":"https://submission.nature.com/new-submission/280/3","title":"Cancer Chemotherapy and Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"82db4961-b0ad-4697-a443-e685afd77e48","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-15T16:04:30+00:00","versionOfRecord":{"articleIdentity":"rs-6602839","link":"https://doi.org/10.1007/s00280-025-04800-w","journal":{"identity":"cancer-chemotherapy-and-pharmacology","isVorOnly":false,"title":"Cancer Chemotherapy and Pharmacology"},"publishedOn":"2025-09-12 15:57:12","publishedOnDateReadable":"September 12th, 2025"},"versionCreatedAt":"2025-05-15 10:24:12","video":"","vorDoi":"10.1007/s00280-025-04800-w","vorDoiUrl":"https://doi.org/10.1007/s00280-025-04800-w","workflowStages":[]},"version":"v1","identity":"rs-6602839","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6602839","identity":"rs-6602839","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}