PHA-665752 化学特性,用途語,生産方法
溶解性
In vitro (25℃) DMSO 128 mg/mL (199.49 mM)
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 (K
i = 4 nM; IC
50 = 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 (IC
50s = 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.
化学的特性
Yellow powder crystal
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.
定義
ChEBI: A member of the class of indolones that is 1,3-dihydro-2H-indol-2-one which is substituted by a (2,6-dichlorobenzyl)sulfonyl group at position 5 and by a (1H-pyrrol-2-yl)methylidene group at position 2, the pyrrole rin
of which is substituted by methyl groups at positions 3 and 5, and by a [2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]carbonyl group at position 4 (the Z,R isomer).
生物活性
Potent, selective and ATP-competitive inhibitor of MET kinase (IC 50 values are 9, 68, 200, 1400, 3000, 3800 and 6000 nM for MET, Ron, Flk-1, c-abl, FGFR1, EGFR and c-src respectively and > 10000 nM for IGF-IR, PDGFR, AURORA2, PKA, PKB α , p38 α , MK2 and MK3). Antitumor agent; inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts.
PHA-665752 上流と下流の製品情報
原材料
準備製品