| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| A408812-1ml |
1ml |
现货  |
|
| 英文别名 | 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide |
|---|---|
| 规格或纯度 | 10mM in DMSO |
| 英文名称 | AMG-458 |
| 生化机理 | AMG 458 是一种强效的 c-Met 抑制剂，Ki为 1.2 nM，对细胞中 c-Met 的选择性是 VEGFR2 的约 350 倍。 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 产品介绍 |
AMG-458 是有效的、选择性的 的 c-Met 抑制剂，其对人和小鼠的 Ki 值分别为 1.2 nM 和 2.0 nM。 Information AMG-458 AMG 458 is a potent c-Met inhibitor with K i of 1.2 nM, ~350-fold selectivity for c-Met than VEGFR2 in cells. AMG 458 also inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM. AMG 458 is observed to bind covalently to liver microsomal proteins from rats and humans in the absence of NADPH. AMG 458 is believed to react with thiol groups in proteins, producing a methoxy quinoline thioether conjugate. A recent study shows that the constitutive phosphorylation of c-Met in H441 is abrogated by AMG 458. The basal and HGF-induced phosphorylation of c-Met in A549 is attenuated by AMG 458. The combination of radiation therapy and AMG 458 treatment is found to synergistically increase apoptosis in the H441 cell line by reduction of p-Akt and p-Erk levels, but not in A549. In vivo AMG 458 is metabolically stable in the liver microsomes of mouse, rat, dog, monkey, and human with low intrinsic clearances (Clint: <5, 62, 8, 8, 18 (μL/min)/mg, respectively). When administered orally, AMG 458 achieves remarkably high bioavailability in all species tested. Oral dosing of AMG 458 inhibits HGF-mediated c-Met phosphorylation with an approximate ED90 of 30 mg/kg and an associated plasma exposure of approximately 15 μM at 6 hours. AMG 458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d.with no adverse effect on body weight. High concentrations of AMG 458 in some organs may produce toxicity via oxidative stress. cell lines： Concentrations： Incubation Time： Powder Purity:≥99% |
| ALogP | 3.125 |
|---|---|
| hba_count | 6 |
| HBD Count | 1 |
| Rotatable Bond | 8 |
| 分子类型 | 小分子 |
|---|---|
| Canonical SMILES | COC1=CC2=NC=CC(=C2C=C1)OC3=CN=C(NC(=O)C4=C(C)N(CC(C)(C)O)N(C4=O)C5=CC=CC=C5)C=C3 |
| 分子量 | 539.58 |
| Reaxy-Rn | 12745427 |
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=12745427&ln= |
| DMSO(mg / mL) Max Solubility | 21 |
|---|---|
| DMSO(mM) Max Solubility | 38.92 |
| Water(mg / mL) Max Solubility | <1 |
| Reaxy-Rn | 12745427 |
|---|---|
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=12745427&ln= |
| Concentration | 9-11（mmol/L） |
|---|---|
| Proton NMR spectrum | Conforms to Structure |
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