PHA-665752 | CAS:477575-56-7

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Name:PHA-665752; 
Cat. No. :CS-0137
CAS No. :477575-56-7
Formula:C32H34Cl2N4O4S
M. Wt. : 641.61
Solubility:10 mM in DMSO

PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM, >50-fold selectivity for c-Met than RTKs or STKs.IC50 value: 9 nMTarget: c-Metin vitro: PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently 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 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of 85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1 [3].

Puri N, et al. A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res, 2007, 67(8), 3529-3534. Ma PC, et al. A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res, 2005, 11(6), 2312-2319. Tsubaki M, et al. Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells. Oncotarget. 2017 Jun 13;8(24):38717-38730. Christensen JG, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res, 2003, 63(21), 7345-7355.