切换导航

Trametinib (GSK1120212)

现货
Catalog No.
A3018
MEK1和MEK2抑制剂
组合的产品项目
规格价格库存 数量
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

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Trametinib (also known as GSK1120212 or JTP 74057), originally identified as a p15 inductive compound, is a novel and potent allosteric inhibitor of MEK kinase, which exhibits ATP non-competitive inhibition against MEK1 and MEK2 kinase. It has demonstrated broad antitumor activities in a variety of tumor xgenograft models, including HT-29 and COLO205 colorectal tumor cell lines. Trametinib induces expression of p15 and p27, reduces cyclin D1 levels, and causes dephosphorylation of RB protein and G1-phase arrest with a reduction of TS expression in HT-29 cells. It also effectively inhibits p-ERK 1/2 resulting in cell growth inhibition in tumor cell lines harboring B-RAF mutant.

Reference

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

文献引用

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt615.39
Cas No.871700-17-3
FormulaC26H23FIN5O4
SynonymsTrametinib, GSK-1120212, GSK1120212, Mekinist, JTP74057, JTP-74057
Solubility≥15.38mg/mL in DMSO
Chemical NameN-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
SDFDownload SDF
Canonical SMILESCC1=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
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。

试验操作

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.

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        

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)