生物活性
BMS-777607是一种Met相关的抑制剂,作用于c-Met, Axl, Ron和Tyro3时,IC50分别为3.9 nM, 1.1 nM, 1.8 nM和4.3 nM,作用于Met相关靶点比作用于Lck, VEGFR-2,和TrkA/B选择性高40倍,比作用于其他受体和非受体激酶选择性高500多倍。BMS-777607是ATP竞争性Met激酶选择性抑制剂,有效抑制c-Met自磷酸化,作用于GTL-16细胞裂解物, IC50为20 nM,且选择性抑制Met驱动的肿瘤细胞系如GTL-16细胞系, H1993和 U87增殖。 BMS-777607 作用于DU145前列腺癌细胞,抑制肝细胞生长因子 (HGF)引起的c-Met自磷酸化, IC50<1 nM 。BMS 777607对肿瘤细胞生长作用效果不大,但是作用于PC-3 和DU145 细胞,抑制HGF诱导的细胞分散。
化学数据
分子量 | 512.89 |
分子式 | C25H19ClF2N4O4 |
CAS号 | 1196681-44-3 |
纯度 | 99.50% |
溶解性(25°C) | DMSO 40 mg/mL |
储存和运输条件 | 固体粉末: -20°C 冷藏长期储存 常温运输及临时存放 |
实验操作 来自于公开的文献,仅供相同实验参考(如实验材料、目的不同,请参考其他文献)
细胞实验 |
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细胞系 | PC-3 cell line |
方法 | Cell proliferation and cell death
Cells were seeded in a 96-well plate at a density of 5 × 103 cells per well and exposed to serial dilutions of BMS-777607 for 1 hour. HGF (25 ng/mL) was then added and the cells were incubated (drug plus HGF) for a period of 96 hours. At the end of the treatment period, the tumor cells were exposed to WST-8 (MTT assay reagent) in a Cell Counting kit (Donjindo Molecular Technologies) according to the manufacturer's instruction, and absorbance was determined at 450 nm colorimetrically. Cell proliferation (%) was calculated as the ratio of absorbance from treated sample to the nontreated control. Cell death was examined by trypan blue exclusion, and positively stained (dead) cells were scored using a hemocytometer. |
浓度 | 0, 0.1, 0.3, 1, 3, 10 μM |
处理时间 | 96 h |
动物实验 |
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动物模型 | C3H/HeJ mice with KHT lung tumor model |
配制 | DMSO |
剂量 | 25mg/kg daily |
给药处理 | oral gavage |
不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
动物 A的Km系数 |
例如,依据体表面积折算法,将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量,需要将20 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
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1 mM | 1.9497 mL | 9.7487 mL | 19.4974 mL |
5 mM | 0.3899 mL | 1.9497 mL | 3.8995 mL |
10 mM | 0.195 mL | 0.9749 mL | 1.9497 mL |