产品说明书
Mirdametinib
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同义名 : | PD0325901;PD325901 |
| CAS号 : | 391210-10-9 | |
| 货号 : | A370482 | |
| 分子式 : | C16H14F3IN2O4 | |
| 纯度 : | 99%+ | |
| 分子量 : | 482.193 | |
| MDL号 : | MFCD08435926 | |
| 存储条件： |
粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 55 mg/mL(114.06 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： |
5%DMSO+40%PEG300+5%Tween80+50%water 5 mg/mL |
| 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. Also MEK itself can be phosphorylated and activated through Ras when the upstream signaling is activated by extracellular stimuli, including growth factors, hormones etc.. PD0325901 is a MEK1/2 with IC50 value of 0.33nM[1]. PD0325901 showed more potency to cell lines harboring BRAF-mutation , including SKMEL28, SKMEL3, SKMEL19, SKMEL1, MALME3M, Colo205 and DU4475, with IC50 values below 10nM, compared with RAS/BRAF-WT cells with IC50>100nM. Meanwhile, dose-dependent decreased p-ERK and Cyclin D1 by PD0325901 can also be observed in these BRAF-mutant cells at concentration>10nM. These suggested that the BRAF mutation may confer the preferential sensitivity of cell lines to MEK inhibition by PD0325901. Consistent with the cellular studies, oral administration with PD0325901 suppressed the tumor growth in mice xenograft SKMEL28 harboring BRAF-V600E mutation at both dose of 5mg/kg and 25mg/kg, accompanied with decrease of p-ERK, Cyclin D1, RB and increased p27. In contrast, treatment with PD0325901 suppressed tumor growth in SKMEL31 (RAS/RAF-WT) xenografts only at high dose (25mg/kg) or even showed no effect in BT-474 (RAS/RAF-WT) xenografts at both dose, regardless the decreased p-ERK by PD0325901[2]. Also it is found that PD0325901 can enhance generation of iPSCs[3]. | ||
| 作用机制 | PD0325901 is a derivative of CI-1040, which is a non-competitive inhibitor of MEK1/2.[2] | ||
| 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 A101D cell | Growth inhibition assay | Inhibition of human A101D cell growth in a cell viability assay, IC50=11.45 nM. | SANGER | ||
| human A375 cell | Growth inhibition assay | Inhibition of human A375 cell growth in a cell viability assay, IC50=2.69 nM. | SANGER | ||
| human A375 cells | Proliferation assay | 72 h | Antiproliferative activity against human A375 cells expressing BRAF V600E mutant after 72 hrs by Cell titer-glo assay, IC50=13 nM. | 23474388 | |
| 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 |
| NCT03170206 | Lung Cancer | Phase 1 Phase 2 | Recruiting | March 31, 2024 | United States, Massachusetts ... 展开 >> Dana Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 Contact: Geoffrey Shapiro, MD, PhD 617-632-4942 Principal Investigator: Geoffrey Shapiro, MD Massachusetts General Hospital Not yet recruiting Boston, Massachusetts, United States, 02215 Contact: Rebecca Heist, MD 617-726-1838 Principal Investigator: Rebecca Heist, MD 收起 << |
| NCT02510001 | Solid Tumor C... 展开 >>olorectal Cancer 收起 << | Phase 1 | Active, not recruiting | September 2019 | United Kingdom ... 展开 >> Oxford University Hospital NHS Trust Oxford, United Kingdom, OX3 7LE 收起 << |
| NCT01347866 | - | Terminated(Refer to Detailed D... 展开 >>escription for documentaion of Termination Statement.) 收起 << | - | - | |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.07mL 0.41mL 0.21mL |
10.37mL 2.07mL 1.04mL |
20.74mL 4.15mL 2.07mL |
