Trametinib又称为GSK1120212、JTP-74057，是一种高特异性的、非ATP竞争的MEK1/2抑制剂，IC50分别为0.92 nM和1.8 nM，但不抑制其他98种激酶，如c-Raf、B-Raf、ERK1/2和MEK5。Trametinib在体内外都表现出抗肿瘤活性，抑制结肠癌细胞和大部分BRAFV600E黑素瘤细胞生长，降低ERK磷酸化和cyclin D1蛋白表达，p15INK4b和/或p27KIP1上调。在HT-29和COLO205移植瘤小鼠体内，Trametinib抑制肿瘤生长。另外，Trametinib具有显著的抗关节炎作用。
参考文献
[1] Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 39(1): 23-31 (2011).
[2] Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide. Inflamm Res, 61(5): 445-454 (2012).
[3] Greger JG, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 11(4):909-920 (2012).
[4] Khalili JS, et al. Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner. Clin Cancer Res, 18(16): 4345-4355 (2012).
[5] King AJ, et al. Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions. PLoS ONE 8(7): e67583 (2013).
[6] Lugowska I, et al. Trametinib: a MEK inhibitor for management of metastatic melanoma. Onco Targets Ther. 8: 2251–2259 (2015).
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注意事项
1）为了您的安全和健康，请穿实验服并戴一次性手套操作。
2）粉末溶解前请先短暂离心，以保证产品全在管底。
3）本产品仅用于科研用途，禁止用于人身上。
使用浓度
【具体使用浓度请参考相关文献，并根据自身实验条件（如实验目的，细胞种类，培养特性等）进行摸索和优化。】
相关实验（数据来自于公开发表的文献，仅供参考）
（一）细胞实验（体外研究）
为检测trametinib在体外细胞中的作用，用dabrafenib处理HCT-116细胞1 h，然后加入不同浓度trametinib（0， 0.5， 5.0，50 nM），dabrafenib诱导pERK上调，而trametinib显著抑制ERK双磷酸化，作用方式为剂量依赖型。[5]
（二）动物实验（体内研究）
体内实验中，给A375P 移植瘤小鼠单独或联合口服dabrafenib（30 mg/kg）、trametinib（0.3 mg/kg），与单独使用某种药物相比，dabrafenib 与trametinib联合作用显著肿瘤生长。[5]
参考文献
[1] Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 39(1): 23-31 (2011).
[2] Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide. Inflamm Res, 61(5): 445-454 (2012).
[3] Greger JG, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 11(4):909-920 (2012).
[4] Khalili JS, et al. Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner. Clin Cancer Res, 18(16): 4345-4355 (2012).
[5] King AJ, et al. Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions. PLoS ONE 8(7): e67583 (2013).
[6] Lugowska I, et al. Trametinib: a MEK inhibitor for management of metastatic melanoma. Onco Targets Ther. 8: 2251–2259 (2015).
