Trametinib (GSK1120212)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 615.39 |
| Cas No. | 871700-17-3 |
| Formula | C26H23FIN5O4 |
| Synonyms | Trametinib, GSK-1120212, GSK1120212, Mekinist, JTP74057, JTP-74057 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥15.38 mg/mL in DMSO |
| Chemical Name | N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide |
| SDF | Download SDF |
| Canonical 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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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°C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°C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. |
|
| 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 | ||||
质量控制和MSDS
- 批次:
化学结构
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