{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:54:12Z","timestamp":1772744052584,"version":"3.50.1"},"reference-count":13,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA182248"],"award-info":[{"award-number":["R21CA182248"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Wortmannin is a potent covalent inhibitor of PI3K that shows substantial in vivo toxicity and thus is unsuitable for systemic therapeutic applications. One possible approach to minimize systemic toxicity is to generate a latent wortmannin pro-drug that will be selectively activated in target tissues. To test this approach, a wortmannin derivative with a leucine linker attached to C20 has been synthesized and tested for inhibition of PI3K activity in prostate cancer cells. Analysis of PI3K pathway inhibition by Wormannin-Leu (Wn-L) and intact Wortmannin (Wn) showed that attachment of Leu at C-20 decreased potency of PI3K pathway inhibition 10-fold compared to intact wortmannin, yet exceeded the potency of a competitive PI3K inhibitor LY294002.<\/jats:p>","DOI":"10.3390\/molecules23071791","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T03:24:27Z","timestamp":1532316267000},"page":"1791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and PI3 Kinase Inhibition Activity of a Wortmannin-Leucine Derivative"],"prefix":"10.3390","volume":"23","author":[{"given":"William","family":"Cantrell","sequence":"first","affiliation":[{"name":"Medicinal and Process Chemistry, Pharmaceutical Development and Biomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, P.O. Drawer 28510, San Antonio, TX 78228, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio A.","family":"Menchaca","sequence":"additional","affiliation":[{"name":"Medicinal and Process Chemistry, Pharmaceutical Development and Biomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, P.O. Drawer 28510, San Antonio, TX 78228, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Kulik","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA"},{"name":"Life Sciences Program, College of Science, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Welker","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.critrevonc.2015.07.005","article-title":"Targeting PI3K\/Akt\/mTOR signaling pathway in the treatment of prostate cancer radioresistance","volume":"96","author":"Chang","year":"2015","journal-title":"Crit. 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