1021920-32-0Relevant articles and documents
Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase
Mortensen, Deborah S.,Sapienza, John,Lee, Branden G.S.,Perrin-Ninkovic, Sophie M.,Harris, Roy,Shevlin, Graziella,Parnes, Jason S.,Whitefield, Brandon,Hickman, Matt,Khambatta, Gody,Bisonette, Rene R.,Peng, Sophie,Gamez, Jim C.,Leisten, Jim,Narla, Rama Krishna,Fultz, Kimberly E.,Sankar, Sabita
supporting information, p. 1588 - 1591 (2013/04/10)
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.
