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In this study, we applied an artificial intelligence\u2010based structure generation using the DeepSARM methodology to create novel scaffold series and to augment medicinal chemistry capabilities. Samotolisib, a PI3K\/mTOR dual inhibitor featuring a tricyclic scaffold, was selected as a model ligand. Following DeepSARM\u2010guided structure generation and ligand\u2010based virtual screening, several candidate compounds with simplified scaffolds were identified. Notably, one top\u2010ranked virtual hit\n                    <jats:bold>6<\/jats:bold>\n                    was selected and further optimized into a simplified tool compound\n                    <jats:bold>6A<\/jats:bold>\n                    for experimental validation. Subsequent synthesis and in vitro evaluation led to the identification of a validated hit bearing a novel nontricyclic scaffold.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70362","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:12:05Z","timestamp":1783566725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Molecular Scaffold Generation of PI3K\/mTOR Inhibitors Using DeepSARM and Ligand\u2010Based Virtual Screening Approaches"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1982-0407","authenticated-orcid":false,"given":"Kenichiro","family":"Shimokawa","sequence":"first","affiliation":[{"name":"Chordia Therapeutics Inc.  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi N.","family":"Imai","sequence":"additional","affiliation":[{"name":"Chordia Therapeutics Inc.  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