GDC-0349

GDC-0349 is a potent inhibitor of the mammalian target of rapamycin (mTOR, Ki = 3.8 nM). It is selective for mTOR over a panel of 266 kinases at a concentration of 1 µM. GDC-0349 inhibits proliferation of PC3 prostate cancer cells in vitro (EC50 = 270 nM) and induces caspase-dependent apoptosis in head and neck squamous cell carcinoma (HNSCC) cells via inhibition of mTOR complex 1 (mTORC1) and mTORC2 and induction of autophagy. Oral administration of GDC-0349 (10-80 mg/kg) inhibits tumor growth in MCF7-neo/Her-2 breast and PC3 prostate cancer mouse xenograft models in a dose-dependent manner. It also reduces tumor growth in an A549 lung cancer mouse xenograft model when administered in combination with the PI3K inhibitor GDC-0941 (Cay-11600) or the MEK inhibitor cobimetinib (GDC-0973, Cay-19563).Formal Name: N-ethyl-N'-[4-[5,6,7,8-tetrahydro-4-[(3S)-3-methyl-4-morpholinyl]-7-(3-oxetanyl)pyrido[3,4-d]pyrimidin-2-yl]phenyl]-urea. CAS Number: 1207360-89-1. Molecular Formula: C24H32N6O3. Formula Weight: 452.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:9): 0.1 mg/ml, Ethanol: 10 mg/ml. lambdamax: 297 nm. SMILES: C[C@H]1COCCN1C2=NC(C3=CC=C(NC(NCC)=O)C=C3)=NC4=C2CCN(C5COC5)C4. InChi Code: InChI=1S/C24H32N6O3/c1-3-25-24(31)26-18-6-4-17(5-7-18)22-27-21-12-29(19-14-33-15-19)9-8-20(21)23(28-22)30-10-11-32-13-16(30)2/h4-7,16,19H,3,8-15H2,1-2H3,(H2,25,26,31)/t16-/m0/s1. InChi Key: RGJOJUGRHPQXGF-INIZCTEOSA-N.