PHA-665752

The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor, have been implicated in the development and progression of several human cancers. PHA-665752 is an ATP-competitive, active-site inhibitor of the catalytic activity of c-Met kinase (Ki = 4 nM, IC50 = 9 nM). It exhibits >50-fold selectivity for c-Met over a panel of tyrosine and serine/threonine kinases. PHA-665752 can inhibit c-Met phosphorylation, as well as cell proliferation and cell motility, of various tumor cells (IC50s = 18-50 nM). It also inhibits signal transduction downstream of c-Met, interfering with the activation of Gab-1 adaptor protein, ERK1/2, Akt, STAT3, PLC-gamma, and focal adhesion kinase in multiple tumor cell lines. In a gastric carcinoma xenograft model, 25 mg/kg PHA-665752 was shown to reduce tumor growth in mice by inhibiting c-Met activation.Formal Name: (3Z)-5-[[(2,6-dichlorophenyl)methyl]sulfonyl]-3-[[3,5-dimethyl-4-[[(2R)-2-(1-pyrrolidinylmethyl)-1-pyrrolidinyl]carbonyl]-1H-pyrrol-2-yl]methylene]-1,3-dihydro-2H-indol-2-one. CAS Number: 477575-56-7. Molecular Formula: C32H34Cl2N4O4S. Formula Weight: 641.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 10 mg/ml, Ethanol: 1 mg/ml. lambdamax: 309, 439 nm. SMILES: O=C1/C(C2=CC(S(CC3=C(Cl)C=CC=C3Cl)(=O)=O)=CC=C2N1)=C\C4=C(C)C(C(N5[C@@H](CN6CCCC6)CCC5)=O)=C(C)N4. InChi Code: InChI=1S/C32H34Cl2N4O4S/c1-19-29(35-20(2)30(19)32(40)38-14-6-7-21(38)17-37-12-3-4-13-37)16-24-23-15-22(10-11-28(23)36-31(24)39)43(41,42)18-25-26(33)8-5-9-27(25)34/h5,8-11,15-16,21,35H,3-4,6-7,12-14,17-18H2,1-2H3,(H,36,39)/b24-16-/t21-/m1/s1. InChi Key: OYONTEXKYJZFHA-SSHUPFPWSA-N.