PHA-665752

PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (K_i=4 nM; IC₅₀=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity^[1][2]. IC50 & Target: Ki: 4 nM^[1]
IC50: 9 nM (c-Met)^[1] In Vitro: PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a K_i of 4 nM and an IC₅₀ of 9 nM^[1].
PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated^[1].
PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and hepatocyte growth factor (HGF)^[1].
PHA-665752 inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines^[1].
PHA-665752 (0-1.25 μM; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells^[1].
PHA-665752 (0-1.25 μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells^[1].
PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells^[1].
In Vivo: PHA-665752 (7.5-30 mg/kg/day; i.v. ; for 9 days) exhibits statistically significant dose-dependent tumor growth inhibition of 68%, 39%, and 20% of vehicle control at the 30 mg/kg/day, 15 mg/kg/day, and 7.5 mg/kg/day doses, respectively^[1].
PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model^[1].