MK-8353 (SCH900353)
规格
| Cas Number | 1184173-73-6 |
| 规格或纯度 | Moligand™, 10mM in DMSO |
| 级别 | Moligand™ |
| 包装 | 1ml |
产品信息
| 品牌 | 阿拉丁 |
| 浓度 | 10mM in DMSO |
| Action Type | 抑制剂 |
| Mechanism Of Action | 丝裂原活化蛋白激酶 1 抑制剂；丝裂原活化蛋白激酶 3 抑制剂 |
| 简短描述 | ERK抑制剂 |
| 英文简短描述 | ERK Inhibitors |
| 过滤标签 | Compound libraries |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 生化和生理学机理 | MK-8353（SCH900353）是一种口服生物利用度高、选择性强的 ERK 抑制剂，在体外可抑制活化的 ERK1 和 ERK2，IC50 值分别为 23.0 nM 和 8.8 nM（IMAP 激酶测定），也可抑制非活化的 ERK2，IC50 值为 0.5 nM（MEK1-ERK2 偶联测定）。 |
| 英文描述 |
Information MK-8353 (SCH900353) MK-8353 (SCH900353) is an orally bioavailable, selective, and potent ERK inhibitor that inhibits activated ERK1 and ERK2 in vitro, with IC50 values of 23.0 nM and 8.8 nM, respectively (IMAP kinase assay), and nonactivated ERK2, with an IC50 of 0.5 nM (MEK1-ERK2-coupled assay). Targets ERK2 (Cell-free assay); ERK1 (Cell-free assay) 7 nM; 20 nM In vitro MK-8353 is a potent and selective inhibitor of both active and inactive ERK1 and ERK2 kinases (IC50=20 and 7 nM, respectively). MK-8353 is not a potent inhibitor of human CYPs 1A2, 2C9, 2C19 or 2D6 but inhibits CYP 3A4 (pre-incubation) in vitro and shows inhibition of CYP 3A4 and 2C8 (IC50 = 1.7 & 3.5 μM), which can cause drug-drug interactions when co administered with drugs that are primarily metabolized by CYP 2C8 or 3A4. MK-8353 is a weak inhibitor of hERG current, producing 16% inhibition at 0.6 μM. The IC50 values for inhibiting cell prolifertion are 371, 51, and 23 nM in A2058, HT-29, and Colo-205 cells respectively. In addition to inhibiting the kinase activity of ERK, MK-8353 prevents the phosphorylation of ERK by MEK. MK-8353 demonstrates kinase selectivity over a 227-human kinase panel; no additional kinase in the panel is inhibited by more than 35% at the 0.1 μM concentration, and only 3 kinases (CLK2, FLT4, and Aurora B) are inhibited >50% at the 1.0 μM concentration. In vivo The in vivo pharmacokinetics and metabolism of MK-8353 are evaluated in male CD1 mice, Sprague Dawley (SD) rats, guinea pigs, beagle dogs, and cynomologus monkeys. With the exception of monkeys, MK-8353 shows moderate clearance after IV administration in all species, with a half-life range of 1.3-2.8 hr and a mean residence time range of 1.5-4.0 hr. Acceptable oral bioavailability is seen in mice, rats and dogs (23-80%) but low oral bioavailability in monkeys (2%). The permeability observed in Caco-2 cells was high (135 nm/sec), suggesting that intestinal absorption and permeability in humans should also be high. The steady-state volume of distribution in mice, dogs and monkeys are in the range of 0.9-3.3 L/kg, while in rats it is 0.1 L/kg. MK-8353 displays anti-tumor efficacy in several BRAF-mutant models. Cell Research(from reference) Cell lines：A2058 cells Concentrations：0, 3, 10, 30, 100, 300 nM Incubation Time：24 hours |