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Trametinib (GSK1120212)MEK1和MEK2抑制剂

Trametinib (GSK1120212)

产品编号:A3018
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10mM (in 1mL DMSO) ¥550.00 现货
50mg ¥960.00 现货
200mg ¥1,920.00 现货
500mg ¥4,050.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

质量控制

化学结构

Trametinib (GSK1120212)

相关生物数据

GSK1120212
GSK1120212 causes sustained inhibition of ERK1/2 phosphorylation, and differential effects on MEK phosphorylation. SK-MEL-28 and A-375P(F11) (BRAF-mutant) cell lines were treated with 250 nmol/L GSK1120212 (Trametinib) and harvested at the indicated time points.

相关生物数据

Trametinib (GSK1120212)

相关生物数据

Trametinib (GSK1120212)

相关生物数据

Trametinib (GSK1120212)

相关生物数据

Trametinib (GSK1120212)

Trametinib (GSK1120212) Dilution Calculator

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化学性质

CAS号 871700-17-3 SDF Download SDF
别名 Trametinib, GSK-1120212, GSK1120212, Mekinist, JTP74057, JTP-74057
化学名 N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
SMILES CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC(=CC=C4)NC(=O)C)C5CC5
分子式 C26H23FIN5O4 分子量 615.39
溶解度 ≥15.38mg/mL in DMSO 储存条件 Store at -20°C
物理性状 A solid 运输条件 试用装:蓝冰运输。
其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议 为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

生物活性

描述 Trametinib (GSK1120212)是一个高度特异性的、有效的MEK1/2抑制剂,IC50值为0.92 nM/1.8 nM。
靶点 MEK1 MEK2        
IC50 0.92 nM 1.8 nM        

实验操作

细胞实验[1]:

细胞系

HT-29细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

100 nM;72小时

应用

在人结肠癌HT-29细胞的细胞计数试剂盒-8实验中,trametinib处理72小时后具有亚纳摩尔的IC50值。Trametinib处理24小时后剂量依赖地增加G1期细胞数量,减少S期细胞数量,而处理72小时后以剂量依赖的方式诱导细胞凋亡,并诱导G1期阻滞。

动物实验[2]:

动物模型

雄性ICR小鼠

剂量

3 mg/kg/天,口服给药。

应用

GSK1120212可以有效阻断ERK的磷酸化,为了检测其是否抑制适应性生长,小鼠用GSK1120212和/或胰蛋白酶抑制剂camostat mesylate S(TI)处理7天。通过测量胰质量、蛋白、DNA和RNA的含量,表明GSK1120212阻断TI诱导的胰生长。这些结果表明,GSK1120212像PD0325901一样,可以阻断TI诱导的胰适应性生长。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Watanabe M, Sowa Y, Yogosawa M, et al. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5‐fluorouracil on human colon cancer cells. Cancer science, 2013, 104(6): 687-693.

[2] Holtz B J, Lodewyk K B, Sebolt-Leopold J S, et al. ERK Activation is Required for CCK-mediated Pancreatic Adaptive Growth in Mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2014: ajpgi. 00163.2014.

研究更新

1. Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212. Mol Cancer Ther. 2012 Mar;11(3):720-9. doi: 10.1158/1535-7163.MCT-11-0505. Epub 2011 Dec 14.
Abstract
GSK1120212, an inhibitor of MEK1 and MEK2, is sensitive to various cell lines including RAF/RAS mutant solid tumor cell lines, breast cancer cell lines, acute myeloid leukemia cell lines and chronic myeloid leukemia cell lines and is less sensitive to cell lines with an expression pattern suggestive of epithelial-to-mesenchymal transition, where expression of gene DUSP6 was associated with GSK1120212 sensitivity.
3. Trametinib (GSK1120212) in the treatment of melanoma. Expert Opin Pharmacother. 2013 Apr;14(5):619-27. doi: 10.1517/14656566.2013.770475. Epub 2013 Feb 23.
Abstract
Somatic mutations involved in MAPK pathway, including NRAS, BRAF, GNAQ and GNA11, are associated with melanoma. Targeting MEK has the potential to be incorporated into the treatment of melanoma patients with those mutations.
4. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol. 2011 Jul;39(1):23-31. doi: 10.3892/ijo.2011.1015. Epub 2011 Apr 26.
Abstract
GSK1120212 is an inhibitor of MEK1/2 that exhibits antitumor activity against colorectal cancer cells through growth inhibition and induced apoptosis. Addition of an Akt inhibitor or a few standard-of-care agents could enhance the antitumor activity of GSK1120212.

产品描述

Trametinib (GSK1120212,JTP 74057)最初被鉴定是一个p15感应性的化合物,是一种新型有效的MEK激酶抑制剂,以ATP非竞争性的方式抑制MEK1和MEK2。据报道,Trametinib在多种肿瘤异种移植模型(包括HT-29和COLO205结直肠肿瘤细胞系)中展示了广泛的抗肿瘤活性。在HT-29细胞中,Trametinib诱导p15和p27的表达,减少细胞周期蛋白D1的水平,引起RB蛋白的去磷酸化和G1期停滞,并减少TS的表达。在含有B-RAF突变的肿瘤细胞系中,Trametinib也可以有效的抑制ERK 1/2的磷酸化,从而导致细胞生长抑制。

参考文献:
Akintunde Akinleye, Muhammad Furqan, Nikhil Mukhi, Pavan Ravella and Delong Liu.  MEK and the inhibitors: from bench to bedside. Journal of Hematology & Oncology 2013, 6:27
Motoki Watanabe, Yoshihiro Sowa, Mayumi Yogosawa and Toshiyuki Sakai.  Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells. Cancer Sci 2013; 104(6): 687-693