{"paper_id":"381b8770-dfa4-4405-af3f-972c102ecc9d","body_text":"Probing the Dark Chemical Matter Against PDE4 for the Management of Psoriasis Using in-Silico and in-Vivo Approach | 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 Probing the Dark Chemical Matter Against PDE4 for the Management of Psoriasis Using in-Silico and in-Vivo Approach Swapna. B, Satvik Kotha, Divakar Selvaraj, S Ramachandra setty, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5091663/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Mar, 2025 Read the published version in Molecular Diversity → Version 1 posted 12 You are reading this latest preprint version Abstract The potential downsides of standard treatments of Apremilast and Roflumilast include gastrointestinal side effects, the risk of mental episodes, and drug interactions, among other things. The rationale of the study is to pay attention to global efforts by describing currently underexplored chemical space regions. The objective was to investigate PDE4D inhibitors utilizing the dark chemical database. The goal was to address this by conducting a computational analysis that coupled docking with molecular dynamics, phase screening, and compound pharmacokinetics optimisation utilizing machine learning and artificial intelligence, which are key parts of drug discovery and development processes. We established the binding mode and critical residues (GLN-369, ILE-336, PHE-340, and PHE-372) involved in interactions with 1,39,353 dark chemical matter molecules out of which 15 hits were obtained and subjected to artificial intelligence (PK parameters) and MD simulations. RMSD and stable amino acids interact with four promising molecules 027230, 060628, 060576 and 085881. The ligand 085881 was found promising since it inhibits both IL-6 and TNF-alpha with IC50 of 18.41 µM and 34.43 µM respectively. In-vivo Erythema grading showed that 085881 test substances possess mild to moderate antipsoriatic action. PDE4 targets Docking and Dynamics DCM database Deep learning Invitro MTT assay Apremilast Imiquimod Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Mar, 2025 Read the published version in Molecular Diversity → Version 1 posted Editorial decision: Revision requested 06 Nov, 2024 Reviews received at journal 25 Oct, 2024 Reviews received at journal 24 Oct, 2024 Reviews received at journal 21 Oct, 2024 Reviewers agreed at journal 20 Oct, 2024 Reviewers agreed at journal 17 Oct, 2024 Reviewers agreed at journal 15 Oct, 2024 Reviewers agreed at journal 15 Oct, 2024 Reviewers invited by journal 15 Oct, 2024 Editor assigned by journal 16 Sep, 2024 Submission checks completed at journal 16 Sep, 2024 First submitted to journal 15 Sep, 2024 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-5091663\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":374734530,\"identity\":\"7d481e7d-0446-45c4-9627-5c8f16b6f499\",\"order_by\":0,\"name\":\"Swapna. 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