WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205795
Description: ZSTK474 is a novel orally applicable phosphoinositide 3-kinase-specific inhibitor that strongly inhibits cancer cell proliferation. Combination treatment using X-rays then ZSTK474 given orally for 8 days, starting 24h post-irradiation, significantly enhanced cell growth inhibition. The combined effect was also observed for clonogenic survival with continuous ZSTK474 treatment. Western blot analysis showed enhanced phosphorylation of Akt and GSK-3β by X-irradiation, whereas phosphorylation was inhibited by ZSTK474 treatment alone. Treatment with ZSTK474 after X-irradiation also inhibited phosphorylation, and remarkably inhibited xenograft tumor growth.
MedKoo Cat#: 205795
Chemical Formula: C19H21F2N7O2
Exact Mass: 417.17248
Molecular Weight: 417.41255
Elemental Analysis: C, 54.67; H, 5.07; F, 9.10; N, 23.49; O, 7.67
Synonym: ZSTK474; ZSTK-474; ZSTK 474;.
IUPAC/Chemical Name: 4,4'-(6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine
InChi Key: HGVNLRPZOWWDKD-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H21F2N7O2/c20-15(21)16-22-13-3-1-2-4-14(13)28(16)19-24-17(26-5-9-29-10-6-26)23-18(25-19)27-7-11-30-12-8-27/h1-4,15H,5-12H2
SMILES Code: FC(C1=NC2=CC=CC=C2N1C3=NC(N4CCOCC4)=NC(N5CCOCC5)=N3)F
Z STK474 directly inhibited PI3K activity more efficiently than the PI3K inhibitor LY294002. At concentrations of 1 microM, ZSTK474 and LY2194002 reduced PI3K activity to 4.7% (95% confidence interval [CI] = 3.2% to 6.1%) and 44.6% (95% CI = 38.9% to 50.3%), respectively, of the untreated control level. Molecular modeling of the PI3K-ZSTK474 complex indicated that ZSTK474 could bind to the ATP-binding pocket of PI3K. ZSTK474 inhibited phosphorylation of signaling components downstream from PI3K, such as Akt and glycogen synthase kinase 3beta, and mediated a decrease in cyclin D1 levels. ZSTK474 administered orally to mice had strong antitumor activity against human cancer xenografts without toxic effects in critical organs. Akt phosphorylation was reduced in xenograft tumors after oral administration of ZSTK474. CONCLUSION: ZSTK474 is a new PI3K inhibitor with strong antitumor activity against human cancer xenografts without toxic effects in critical organs. ZSTK474 merits further investigation as an anticancer drug. (source: J Natl Cancer Inst. 2006 Apr 19;98(8):545-56.)
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