Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370257 | Bioorganic & Medicinal Chemistry Letters | 2011 | 7 Pages |
Abstract
We report here the discovery of a novel series of selective mTOR kinase inhibitors. A series of imidazo[4,5-b]pyrazin-2-ones, represented by screening hit 1, was developed into lead compounds with excellent mTOR potency and exquisite kinase selectivity. Potent compounds from this series show >1000-fold selectivity over the related PI3Kα lipid kinase. Further, compounds such as 2 achieve mTOR pathway inhibition, blocking both mTORC1 and mTORC2 signaling, in PC3 cancer cells as measured by inhibition of pS6 and pAkt (S473).
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Deborah S. Mortensen, Sophie M. Perrin-Ninkovic, Roy Harris, Branden G.S. Lee, Graziella Shevlin, Matt Hickman, Gody Khambatta, Rene R. Bisonette, Kimberly E. Fultz, Sabita Sankar,