کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370317 | 981816 | 2013 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We report here the discovery of a novel series of selective mTOR kinase inhibitors and the identification of CC214-2, a compound with demonstrated anti-tumor activity upon oral dosing in a PC3 prostate cancer xenograft model. A series of 4,6-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were discovered through a core modification of our original compound series. Analogs from this series have excellent mTOR potency and maintain selectivity over the related PI3Kα lipid kinase. Compounds such as CC214-2 were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC3 cancer cells, in vitro and in vivo.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 6, 15 March 2013, Pages 1588–1591
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 6, 15 March 2013, Pages 1588–1591
نویسندگان
Deborah S. Mortensen, John Sapienza, Branden G.S. Lee, Sophie M. Perrin-Ninkovic, Roy Harris, Graziella Shevlin, Jason S. Parnes, Brandon Whitefield, Matt Hickman, Gody Khambatta, Rene R. Bisonette, Sophie Peng, Jim C. Gamez, Jim Leisten,