PHA-665752

用途強 力 で 選択的 な MET キ ナ ー ゼ 阻 害 剤（IC50 = 9 nmol/l（MET），68 nmol/l（Ron），200 nmol/l（Flk-1），1,400 nmol/l（c-abl），3,000 nmol/l（FGFR1），3,800 nmol/l（EGFR），6,000 nmol/l（c-src）。ATP 競合性です。抗がん作用を示します。

用途強力で選択的な MET キナーゼ阻害剤（IC50 = 9 nM（MET），68 nM（Ron），200 nM（Flk-1）， 1,400 nM（c-abl），3,000 nM（FGFR1），3,800 nM（EGFR），6,000 nM（c-src）。ATP 競合 性です。抗がん作用を示します。

説明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-γ, 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.

使用PHA-665752 ia a c-Met kinase inhibitor. PHA-665752 is ATP-competitive, an active-site inhibitor with greater than 50-fold selectivity for c-Met vs a panel of tyrosine and serine-threonine kinases.