product name GDC-0349
Description: GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR with Ki of 3.8 nM, it has 790-fold inhibitory effect against PI3Kα and other 266 kinases. GDC-0349 inhibited mTOR downstream markers such as phospho-Akt(s473) and phospho-4EBP1 in an in vivo PK/PD study model in mouse, which is consistent with an inhibition of mTORC1/mTORC2 complexes. GDC-0349 inhibited tumor growth in a dose-dependent manner when dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model (PI3K mutation).
References: J Med Chem. 2013 Apr 11;56(7):3090-101; ACS Med Chem Lett. 2012 Nov 29;4(1):103-7.
452.55
Formula
C24H32N6O3
CAS No.
1207360-89-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 91 mg/mL (201.1 mM)
Water: <1 mg/mL
Ethanol: 6 mg/mL (13.3 mM)
Solubility (In vivo)
Synonyms
RG-7603
other peoduct :
| In Vitro |
Kinase Assay: Cell Assay: 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. |
|---|---|
| In Vivo | 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). |
| Animal model | MCF7-neo/Her2 tumor xenograft |
| Formulation & Dosage | Formulated in 0.5% methylcellulose/0.2% Tween 80; 10, 20, 30, 40,50, 60, 70, 80 mg/kg; p.o. |
| References | J Med Chem. 2013 Apr 11;56(7):3090-101. |
