{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:52:39Z","timestamp":1793649159758,"version":"4.5.1"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T00:00:00Z","timestamp":1697328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The PI3K\/AKT\/mTOR pathway is one of the most common dysregulated signaling cascade responses in human cancers, playing a crucial role in cell proliferation and angiogenesis. Therefore, the development of anticancer drugs targeting the PI3K and mTOR pathways has become a research hotspot in cancer treatment. In this study, the PI3K selective inhibitor GDC\u20100941 was selected as a lead compound, and 28 thiophenyl\u2010triazine derivatives with aromatic urea structures were synthesized based on scaffold hopping, serving as a novel class of PI3K\/mTOR dual inhibitors. The most promising compound <jats:bold>Y\u20102<\/jats:bold> was obtained through antiproliferative activity evaluation, kinase inhibition, and toxicity assays. The results showed that <jats:bold>Y\u20102<\/jats:bold> demonstrated potential inhibitory effects on both PI3K kinase and mTOR kinase, with IC<jats:sub>50<\/jats:sub> values of 171.4 and 10.2\u2009nM, respectively. The inhibitory effect of <jats:bold>Y\u20102<\/jats:bold> on mTOR kinase was 52 times greater than that of the positive drug GDC\u20100941. Subsequently, the antitumor activity of <jats:bold>Y\u20102<\/jats:bold> was verified through pharmacological experiments such as AO staining, cell apoptosis, scratch assays, and cell colony formation. The antitumor mechanism of <jats:bold>Y\u20102<\/jats:bold> was further investigated through JC\u20101 experiments, real\u2010time quantitative PCR, and Western blot analysis. Based on the above experiments, <jats:bold>Y\u20102<\/jats:bold> can be identified as a potent PI3K\/mTOR dual inhibitor for cancer treatment.<\/jats:p>","DOI":"10.1002\/ardp.202300403","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T05:45:53Z","timestamp":1697435153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery of novel potent PI3K\/mTOR dual\u2010target inhibitors based on scaffold hopping: Design, synthesis, and antiproliferative activity"],"prefix":"10.1002","volume":"356","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy Jiangxi Science &amp; Technology Normal University Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key 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