Exploring Target-Based Screening, Molecular Dynamics Simulation and Principal Component Analysis for Drug Repurposing in NUT Midline Carcinoma

Exploring Target-Based Screening, Molecular Dynamics Simulation and Principal Component Analysis for Drug Repurposing in NUT Midline Carcinoma | 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 Exploring Target-Based Screening, Molecular Dynamics Simulation and Principal Component Analysis for Drug Repurposing in NUT Midline Carcinoma Ajijur Rehman, Abrar Ahmad, Mohd Wamique, Anchal Trivedi, Aditi Srivastava, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6601284/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 8 You are reading this latest preprint version Abstract Purpose: NMC, a particularly malignant and invasive cancer resulting from the fusion of the NUT and BRD4 genes, yields a fusion protein that influences cell growth and regulates transcription. The deregulation of this protein has been documented in numerous cancerous conditions. The BD1 domain of BRD4-containing proteins has been demonstrated to bind to acetylated lysine residues on histone proteins, thereby impacting gene expression and chromatin remodeling. Methods: The DrugRep database was used for target-based screening (TBS) of FDA-approved drugs. CurPocket, an integrated tool within DrugRep, was employed to automatically identify potential binding pockets, and docking was performed using AutoDock Vina 1.1.2. SwissADME tools were utilized to assess pharmacokinetics and drug-likeness attributes. Additionally, the GROMACS and Galaxy platforms were employed for MD simulations and principal component analysis, respectively. Results: The TBS technique was used to evaluate 100 drug candidates for human intestinal absorption and blood-brain barrier permeability using the Egan-Egg model. 84 met the filtration criteria, and the drug-likeness models narrowed the pool to 48. Toxicophoric parameters, including the PAINS and Brenk alerts, further refined the subset of potential drugs to 39. The lead-likeness criteria identified five drugs, which were evaluated based on binding free energy and hydrogen bond analysis. MD simulation and PCA led to more in-depth evaluations, ultimately leading to the selection of estrone as a potential repurposed drug for NMC. Conclusion: These results indicated that ataluren may be a suitable candidate for the development of a therapeutic drug to treat NMC. However, additional laboratory experiments are required to validate these preliminary findings. NUT midline carcinoma BRD4 Bromodomain Virtual Screening ADME Docking Molecular Dynamics Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 26 Oct, 2025 Reviews received at journal 12 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers agreed at journal 07 Oct, 2025 Reviewers invited by journal 05 Oct, 2025 Editor assigned by journal 07 May, 2025 Submission checks completed at journal 07 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. 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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-6601284","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":530118464,"identity":"bf9bc4bd-48eb-4ebb-9842-3d4e0f837b6c","order_by":0,"name":"Ajijur Rehman","email":"","orcid":"","institution":"NIMS Institute of Allied Medical Sciences \u0026 Technology, NIMS University","correspondingAuthor":false,"prefix":"","firstName":"Ajijur","middleName":"","lastName":"Rehman","suffix":""},{"id":530118465,"identity":"63b37943-5ac1-41fe-8332-e9ed4093317c","order_by":1,"name":"Abrar Ahmad","email":"","orcid":"","institution":"AIMST 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