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We present LinkD, an integrated framework that unifies diffusion-based affinity prediction, proteome-wide selectivity scoring, phenotypic validation, and population-scale clinical evidence. LinkD-Bind predicts binding across 14,981 drugs and 20,385 human targets, ranking first in 8 of 9 BindingDB, Davis, and KIBA evaluations, with the largest gains under cold-start conditions. LinkD-Select recovers 95.3% of known drug-target pairs by combining selectivity scoring and molecular docking. LinkD-Pheno integrates drug-sensitivity and CRISPR dependency data across 960 cancer cell lines, identifying 34 novel drug-gene pairs and recovering \u223c85% of known targets among the top 50 candidates. Across 11.5 million individuals from Mount Sinai and UK Biobank, LinkD-prioritized \u03b2-blockers propranolol (HR 0.82) and carvedilol (HR 0.92) reduced 5-year prostate cancer incidence relative to metoprolol, corroborated by ADRB2 docking and LNCaP growth inhibition. LinkD-Agent, which can effectively orchestrate all evidence layers, is served on a publicly available web platform (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/linkd-agent.onrender.com\/\">https:\/\/linkd-agent.onrender.com\/<\/jats:ext-link>\n                  ), enabling a wide range of users to derive new drug repurposing opportunities through natural language queries.\n                <\/jats:p>","DOI":"10.64898\/2026.04.19.719462","type":"posted-content","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:05:11Z","timestamp":1776895511000},"source":"Crossref","is-referenced-by-count":0,"title":["An Agentic Platform for Drug Repurposing Unified across Molecular, Phenotypic, and Clinical Scales"],"prefix":"10.64898","author":[{"given":"Cheng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Moussaoui","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathiksha","family":"Prabhakaraalva","sequence":"additional","affiliation":[{"name":"Departments of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Departments of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Tisch Cancer Institute; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Merzliakov","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita Jui-Hsien","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabila","family":"Zaman","sequence":"additional","affiliation":[{"name":"Departments of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Departments of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Tisch Cancer Institute; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goutam","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Departments of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Departments of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Tisch Cancer Institute; 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