Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 4, Issue 1, Pages 103-107Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml3003132
Keywords
Mammalian target of rapamycin; mTOR; TDI; urea bioisostere
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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.
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