生物活性
AMG-208是一种高度选择性的c-Met抑制剂，IC50为9 nM。AMG-208 有效抑制激酶c-Met活性，IC50为 9 nM。此外, AMG-208作用于PC3细胞，也抑制HGF调节的 c-Met磷酸化，IC50 为 46 nM。在 NADPH 存在时，AMG-208 和大鼠及人类肝脏微粒温育，造成 C6-phenylarene氧化。
化学数据
| 分子量 | 383.4 |
| 分子式 | C22H17N5O2 |
| CAS号 | 1002304-34-8 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 3 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 |
|---|
| 细胞系 | PC-3 cells |
| 方法 | Cell-based autophosphorylation assay of c-Met.
IC50 measurements of compound activity on HGF-mediated c-Met autophosphorylation were determined in serum-starved PC-3 (human) cells using a quantitative electrochemiluminescent immunoassay. PC3 cells were plated at a density of 20,000 cells/well in 96 well-plates. 24 hours after plating, cells were starved in media containing 0.1% BSA for 18 to 20 hours. Cells were then treated with a 10-point serial dilution of Compound A for one hour at 37℃ followed by stimulation with optimal concentrations of recombinant human HGF for 10 minutes at 37℃. Cells were washed once with PBS and lysed (1% Triton X-100, 50 mM Tris pH 8.0, 100 mM NaCl, 300 μM Na3OV4 and protease inhibitors). Cell lysates were incubated with a biotin-labeled goat–anti-c-Met antibody (BAF358 – for human c-Met, R&D Systems, Minneapolis, MN) for capture followed by a mouse anti-phosphotyrosine antibody 4G10 (Upstate, Charlottesville, VA) and a BV-tagTM labeled anti-mouse IgG (BioVeris Inc., Gaithersburg, MD) as the detection antibody. Levels of c-Met phophorylation were then measured on a BioVeris M-Series instrument. The IC50 values are calculated using Xlfit4-parameter equation. |
| 浓度 | IC50=46 nM |
| 处理时间 | 10 min |
| 动物实验 |
|---|
| 动物模型 | female Balb/c mice |
| 配制 | 2%HPMC, 1%Tween80, in water adjusted to pH 2.2 with HCl |
| 剂量 | 3, 10, or 30 mg/kg |
| 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 |
|---|
| 1 mM | 2.6082 mL | 13.0412 mL | 26.0824 mL |
| 5 mM | 0.5216 mL | 2.6082 mL | 5.2165 mL |
| 10 mM | 0.2608 mL | 1.3041 mL | 2.6082 mL |
