Selumetinib

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Chemical Structure| 606143-52-6 同义名 : 司美替尼 (AZD6244) ;AZD6244;ARRY-142886;ARRY886;NSC 741O78;CL 1,040
CAS号 : 606143-52-6
货号 : A351367
分子式 : C17H15BrClFN4O3
纯度 : 99%+
分子量 : 457.681
MDL号 : MFCD11977472
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(43.7 mM)，配合低频超声助溶，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
动物实验配方：

4% DMSO+30% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
靶点

  • MEK2

    MEK2, Kd:530 nM

  • MEK1

    MEK1, Kd:99 nM

    MEK1, IC50:14 nM
描述 The Ras-Raf-MEK pathway is overactive in many human cancers, such as melanoma and NSCLC. Selumetinib, also called as ARRY-142886 or AZD6244, is a potent and highly selective MEK1/2 inhibitor with IC50 of 14 nM (measured by the catalytic activation of purified His-MEK1 on ERK2). Selumetinib can inhibit the enzymatic activity of MEK1/2 but not the MEK1/2 phosphorylation by Raf. IC50 of Selumetinib to inhibit MEK1/2 phosphorylation on ERK1/2 in cell lines examed is less than 40 nM. In EGFR-overexpressed A431 cells, EGF-induced ERK1/2 phosphorylation can be inhibited by Selumetinib at the concentration < 10 μM in a dose-dependent manner, while no obvious inhibition can be observed in ERK5. In cell growth study, Selumetinib shows more potent in cell lines containing activating B-Raf and Ras mutations (HT-29, Malme-3M, MIA PaCa-2, SK-MEL-2, SK-MEL-28 cells, IC50 values ranging from 59 to 473 nM), while it had no effect on other cell lines examined, including BxPC3, BT474 and Malme-3 cells with no Raf/Ras-mutantion reported. 21-day administration of selumetinib orally, BID, can inhibit the tumour growth up to 70% at the concentration of 100 mg/kg in mice bearing HT-29 tumors and inhibition of phospho-ERK1/2 was seen[1]. Selumetinib is mainly used in the study of melanoma, NSCLC, Neurofibromatosis type 1 etc.[2].
作用机制 Molecular modeling data shows Selumetinib can bind to the allosteric inhibitor binding site in 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 A101D cell Growth inhibition assay Inhibition of human A101D cell growth in a cell viability assay, IC50=240.33 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=31 nM. 23474388
human A549 cell Growth inhibition assay Inhibition of human A549 cell growth in a cell viability assay, IC50=214.13 nM. SANGER
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
NCT00085787 Advanced Cancer Phase 1 Completed - United States, Colorado ... 展开 >> University of Colorado Cancer Center, Anschutz Cancer Center Aurora, Colorado, United States, 80010 United States, Minnesota Mayo Clinic Rochester Rochester, Minnesota, United States, 55905 United States, Pennsylvania Fox Chase Cancer Center Philadelphia, Pennsylvania, United States, 19111 收起 <<
NCT00780676 Breast Cancer Phase 2 Terminated(Closed early for fu... 展开 >>tility.) 收起 << - United States, Texas ... 展开 >> UT MD Anderson Cancer Center Houston, Texas, United States, 77030 收起 <<
NCT02546661 Muscle Invasive Bladder Cancer Phase 1 Recruiting March 27, 2020 -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.92mL

2.18mL

1.09mL

21.85mL

4.37mL

2.18mL
参考文献

[1]Yeh TC, Marsh V, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.

[2]Bernabé R, Patrao A, et al. Selumetinib in the treatment of non-small-cell lung cancer. Future Oncol. 2016 Nov;12(22):2545-2560.

[3]Bartholomeusz C, Oishi T, et al. MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model. Mol Cancer Ther. 2012 Feb;11(2):360-9.

[4]Denton CL, Gustafson DL, et al. Pharmacokinetics and pharmacodynamics of AZD6244 (ARRY-142886) in tumor-bearing nude mice. Cancer Chemother Pharmacol. 2011 Feb;67(2):349-60.