GDC-0349 --- mTOR Inhibitor [1207360-89-1] [1207360-89-1]

Bioss

GDC-0349 --- mTOR Inhibitor [1207360-89-1] [1207360-89-1]

16

1207360-89-1

Research Use Only

Unconjugated

98 - 98.0

C24 H32 N6 O3

452.55

GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR with IC50 ~3.8 nM. It has remarkable selectivity over 266 kinases, including all isoforms of PI3K (less than 25% inhibition when tested at 1 microM against Invitrogen kinase panel). 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 inhibited tumor growth in a dose-dependent manner. It was also efficacious in other xenograft models, including PC3 (PTEN null) and 786-0 (VHL mutant). GDC-0349 inhibited 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. Currently GDC-0349 is in Phase I clinical trials to evaluate the safety and tolerability in patients with locally advanced or metastatic solid tumors or Non-Hodgkins lymphoma.

C[C@H]1COCCN1C1=NC(=NC2CN(CCC1=2)C1COC1)C1=CC=C(C=C1)NC(=O)NCC

-20°C

12161509