GDC-0349

GDC-0349 is a potent small molecule mTOR inhibitor with Ki of 3.8 nM. GDC-0349 inhibits downstream markers of mTOR, including phospho-4EBP1 and phospho-Akt(S473) in an in vivo PK/PD study in mouse, consistent with an inhibition of both mTORC1 and mTORC2 complexes. GDC-0349 inhibits tumor growth in a dose-dependent manner when dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model. GDC-0349 is also efficacious in other xenograft models, including PC3 (PTEN null) and 786-O (VHL mutant). GDC-0349 is currently in a Phase I clinical trials in the treatment with solid tumors or Non-Hodgkin's lymphoma.