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Trametinib DMSO solvate

现货
Catalog No.
A3887
变构MEK1/MEK2 激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 500.00
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50mg
¥ 800.00
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100mg
¥ 1,190.00
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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
1.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
2.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

1. Lee PC, Fang YF, et al. "Targeting PKCδ as a Therapeutic Strategy against Heterogeneous Mechanisms of EGFR Inhibitor Resistance in EGFR-Mutant Lung Cancer." Cancer Cell. 2018 Dec 10;34(6):954-969.e4. PMID:30537515

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt693.53
Cas No.1187431-43-1
FormulaC28H29FIN5O5S
SynonymsGSK-1120212 DMSO solvate;Trametinib;JTP-74057;GSK-1120212;GSK1120212;GSK 1120212;JTP 74057;JTP74057
Solubility≥11.2mg/mL in DMSO with ultrasonic and warming, <5.03mg/mL in H2O, <4.9mg/mL in EtOH
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;methylsulfinylmethane
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.CS(=O)C
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

激酶实验 [1]:

Raf-MEK-ERK级联激酶检测

将非磷酸化髓鞘碱性蛋白 (MBP) 涂覆到ELISA板上。将活性B-Raf/c-Raf与非磷酸化MEK1/MEK2和ERERK2混合于含10 μM ATP和12.5 mM MgCl2的MOPS缓冲液(已含不同浓度的Trametinib)中。使用抗磷酸化MBP抗体测定MBP磷酸化。

细胞实验 [1]:

细胞系

HT-29和COLO205细胞

制备方法

可溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

0、1、10和100 nM;0 ~ 4天

实验结果

Trametinib均能诱导HT-29和COLO205细胞凋亡。在诱导凋亡方面,相对于HT-29细胞,COLO205细胞对Trametinib更敏感。

动物实验 [1]:

动物模型

皮下注射HT-29或COLO205细胞的雌雄BALB/c-nu/nu小鼠

给药剂量

0.3或1 mg/kg;口服给药;每日1次,持续14天

实验结果

口服给予Trametinib(0.3或1 mg/kg,每日1次,持续14天)有效抑制HT-29细胞异种移植肿瘤。此外,在1 mg/kg的剂量下,Trametinib完全抑制肿瘤生长。在COLO205细胞异种移植肿瘤模型中,0.3 mg/kg Trametinib足以抑制肿瘤生长。当剂量为1 mg/kg时,Trametinib使2/3老鼠的肿瘤消退至可检测水平之下。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Yamaguchi T, Kakefuda R, Tajima N, Sowa Y, Sakai T. 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.

质量控制

化学结构

Trametinib DMSO solvate