- Discovery and biological profiling of potent and selective mTOR inhibitor GDC-0349
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Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR. GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.
- Pei, Zhonghua,Blackwood, Elizabeth,Liu, Lichuan,Malek, Shiva,Belvin, Marcia,Koehler, Michael F. T.,Ortwine, Daniel F.,Chen, Huifen,Cohen, Frederick,Kenny, Jane R.,Bergeron, Philippe,Lau, Kevin,Ly, Cuong,Zhao, Xianrui,Estrada, Anthony A.,Truong, Tom,Epler, Jennifer A.,Nonomiya, Jim,Trinh, Lan,Sideris, Steve,Lesnick, John,Bao, Linda,Vijapurkar, Ulka,Mukadam, Sophie,Tay, Suzanne,Deshmukh, Gauri,Chen, Yung-Hsiang,Ding, Xiao,Friedman, Lori S.,Lyssikatos, Joseph P.
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supporting information
p. 103 - 107
(2013/02/26)
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- PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).
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Page/Page column 199
(2010/04/03)
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