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BMS 777607

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Chemical Structure| 1025720-94-8 同义名 : BMS 817378
CAS号 : 1025720-94-8
货号 : A756664
分子式 : C25H19ClF2N4O4
纯度 : 99%+
分子量 : 512.893
MDL号 : MFCD16495773
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 40 mg/mL(77.99 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

4% DMSO+45% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
描述 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]
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 20515943
DU145 0.01 μM Function assay suppresses HGF-induced cell migration 20515943
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01721148 Malignant Solid Tumour Phase 1 Completed - -
NCT00605618 Advanced Solid Tumors Phase 1 Phase 2 Completed - Australia, New South Wales ... 展开 >> Local Institution Camperdown, New South Wales, Australia, 2050 Local Institution Kogarah, New South Wales, Australia, 2217 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.20mL

9.75mL

1.95mL

0.97mL

19.50mL

3.90mL

1.95mL
参考文献

[1]Dai Y, Bae K, et al. Impact of the small molecule Met inhibitor BMS-777607 on the metastatic process in a rodent tumor model with constitutive c-Met activation. Clin Exp Metastasis. 2012 Mar;29(3):253-61.

[2]Wu CC, Weng CS, et al. Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET. Taiwan J Obstet Gynecol. 2019 Jan;58(1):145-152.

[3]Schroeder GM, An Y, et al. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem. 2009 Mar 12;52(5):1251-4.