GDC0349 是一种ATP竞争性的选择性mTOR抑制剂，Ki值为 3.8 nM。它对 PI3Kα 和其他 266 种激酶的抑制作用是 790 倍，可抑制mTORC1和mTORC2复合体。

GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR with Ki of 3.8 nM, 790-fold inhibitory effect against PI3Kα and other 266 kinases. Phase 1.

GDC-0349 has remarkable selectivity over 266 kinases, including all isoforms of PI3K. 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. [1]

GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models. When dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model (PI3K mutation), GDC-0349 inhibits tumor growth in a dose-dependent manner. It is also efficacious in other xenograft models, including PC3 (PTEN null) and 786-O (VHL mutant). [1]

1207360-89-1

C24H32N6O3

452.559

RG-7603

H2O:<1 mgml
Ethanol:6 mg/mL (13.25 mM)
DMSO:84 mg/mL (185.6 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years