GDC-0349

Short Summary : MTOR inhibitor

Category : PI3K/Akt/mTOR Signaling|mTOR

Purity : 0.98

CAS Number : 1207360-89-1

Formula : C24H32N6O3

Molecular Weight : 452.55

SMILE : CCNC(=O)NC1=CC=C(C=C1)C2=NC3=C(CCN(C3)C4COC4)C(=N2)N5CCOCC5C

Solubility : >4.6mg/mL in DMSO

Storage : Store at -20°C

Description : GDC-0349 is a potent, selective, ATP-competitive inhibitor of (Mammalian target of rapamycin) mTOR with Ki value of 3.8nM [1].GDC-0349 is a remarkably selective mTOR inhibitor, with less than 25% inhibition of 266 kinases, including all isoforms of PI3K. GDC-0349 inhibited mTOR downstream markers , involving phospho-Akt(s473) and phospho-4EBP1 in an in vivo PK/PD study in mouse, consistent with an inhibition of mTORC1/mTORC2 complexes [1].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). GDC-0349 was also efficacious in other xenograft models, including PC3 (PTEN null) and 786-0 (VHL mutant). However, GDC-0349 showed only modest tumor growth delay in the A549 mouse xenograft model (KRas mutant, LKB1 deficient) [1].References:[1] Pei, Z.; Blackwood, E.; Liu, L.; Malek, S.; Belvin, M.; Koehler, M. F. T.; Ortwine, D. F.; Chen, H.; Cohen, F.; Kenny, J. R.; Bergeron, P.; Lau,K.; Ly, C.; Zhao, X.; Estrada, A. A.; Truong, T.; Epler, J. A.; Nonomiya, J.; Trinh, L.; Sideris, S.; Lesnick, J.; Bao, L.; Vijapurkar, U.; Mukadam,S.; Tay, S.; Deshmukh, G.; Chen, Y.-H.; Ding, X.; Friedman, L.; Lyssikatos, J. P.Discovery and biological profiling of potent and selective mTOR inhibitor GDC-0349 ACS Med. Chem. Lett. 2013, 4, 103C 107

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