BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM, being 40-fold selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases.
The overexpression and activation of the Met receptor and its ligand HGF (hepatocyte growth factor) are associated with a wide variety of human malignancies, as well as the tumor invasion. BMS-777607 is a multiple Met kinase inhibitor with IC50 values of 1.1 nM, 1.8 nM, 3.9 nM and 4.3 nM for Axl, Ron, Met and Tyro3, respectively, modestly potent to Mer, Flt-3 and Aurora B with IC50 values of 14 nM, 16 nM and 78 nM, as well as inhibited Lck, VEGFR-2, TrkB, TrkA and PKA with IC50>100 nM. BMS-777607 showed anti-proliferative effect on Met-driven H1993 with IC50 value of 150 nM and U87 (glioblastoma, autocrine loop) with IC50 value of 160 nM, but lacking activity against the Met-independent N87 cell line. Exposure to BMS-777607 for 30 min at concentration>33 nM caused reduction of p-Met in a dose-dependent manner in GTL-16 cells. Consistent with the cell growth inhibition assays, an in vivo study showed that once daily oral administration of BMS-777607 at dose of 6.25 mg/kg, 12.5 mg/kg, 25 mg/kg and 50 mg/kg for 14 consecutive days caused tumor growth inhibition in a GTL-16 xenograft model[1].
作用机制
BMS-777607 is an ATP-competitive inhibitor of the Met kinase.[1]
BMS 777607 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
CHRF
10 μM
Function assay
inhibits cell division
25304900
DU145
0.1 μM
Function assay
exhibits inhibitory effect on HGF-induced cell scattering
Australia, New South Wales
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Local Institution
Camperdown, New South Wales, Australia, 2050
Local Institution
Kogarah, New South Wales, Australia, 2217 收起 <<
Australia, New South Wales
... 展开 >>
Local Institution
Camperdown, New South Wales, Australia, 2050
Local Institution
Kogarah, New South Wales, Australia, 2217 收起 <<
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