产品说明书
Pimasertib
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同义名 : | AS703026;MSC1936369B;SAR 245509 |
| CAS号 : | 1236699-92-5 | |
| 货号 : | A199908 | |
| 分子式 : | C15H15FIN3O3 | |
| 纯度 : | 98% | |
| 分子量 : | 431.201 | |
| MDL号 : | MFCD16660676 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 105 mg/mL(243.51 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 |
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| 动物实验配方： |
IP 2% DMSO+2% Tween80+30% PEG300+water 10 mg/mL clear PO 0.5% CMC-Na 11 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 描述 | MEKs, which are members of the MAPKK family, can activate both ERK1 and ERK2 by catalyzing the phosphorylation on T202/Y204. It is found that the tumor growth, like multiple myeloma, and survival, as well as angiogenesis and drug resistance are markedly associated with the MEK/ERK signal transduction pathway. Pimasertib is a potent and selective inhibitor of MEK1/2. As prediction by the inhibition of MEK1/2 kinase activity, incubation with Pimasertib at concentration ranging in 5-2000nM for 1h caused dose-dependent as well as time-dependent, at concentration of 200nM within 72h, decrease of p-ERK1/2 in U266 cells. A further study showed that Pimasertib can targeted multiple myeloma cells in the BMSCs microenvironment specifically through block of MEK/ERK pathway and improved agent. Exposure to Pimasertib at concentration>20nM significantly decreased the secretion of the cytokines induced by adhesion of MM cells to BMSCs, including VEGF and IL-6 in a dose-dependent manner. Treatment with 0.5μM Pimasertib alone over 8h significantly triggered apoptosis, shown as PARP and caspase 3 cleavage in H929 MM cells, as well as increased subG0 and decreased S phase cell population at 0.1μM in both H929 and U266 cells within 72h. Combination of Pimasertib (20nM-20μM) with anti-MM drugs rapamycin (0.1-100nM) for 2 days can augment MM1S cell death. Orally treatment with Pimasertib at dose of both 15mg/kg and 30mg/kg, BID, 5 days per week for 2 weeks, inhibited human MM cell growth in mice bearing H929 MM tumours, accompanied with decreased p-ERK and induced apoptosis. Reduced percentage of CD34+ cells and microvascular density can also be observed in H929 tumours from mice treated with Pimasertib, suggesting the possible inhibitory effect on angiogenesis by Pimasertib in vivo[1]. | ||
| 作用机制 | Pimasertib is an non-ATP competitive inhibitor of MEK1/2.[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 |
| human COLO205 cells | Function assay | Inhibition of MEK1 in human COLO205 cells, IC50=0.00181 μM | 24755426 | ||
| 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 |
| NCT01992874 | Neoplasms | Phase 1 | Completed | - | United States, Massachusetts ... 展开 >> Please Contact U.S. Medical Information Located in Rockland, Massachusetts, United States 收起 << |
| NCT01693068 | N-Ras Mutated Locally Advanced... 展开 >> or Metastasis Malignant Cutaneous Melanoma 收起 << | Phase 2 | Completed | - | - |
| NCT01713036 | Locally Advanced or Metastatic... 展开 >> Solid Tumors 收起 << | Phase 1 | Completed | - | Hungary ... 展开 >> Research Site Budapest, Hungary 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.32mL 0.46mL 0.23mL |
11.60mL 2.32mL 1.16mL |
23.19mL 4.64mL 2.32mL |
| 参考文献 |
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