• 提示：详情请下载说明书。

• 产品描述： Trametinib (GSK1120212, JTP-74057, Mekinist) DMSO solvate 是一种高度特异性的、有效的 MEK1/2 的抑制剂，在无细胞分析中的IC50值为0.92 nM/1.8 nM。Trametinib 可激活自噬并诱导细胞凋亡

• 靶点： MEK1(Cell-free assay):0.92 nM; MEK2(Cell-free assay):1.8 nM;Apoptosis; MEK

• 体外研究：
  GSK1120212 inhibits the phosphorylation of MBP regardless of the isotype of Raf and MEK, with IC50 ranging from 0.92 nM to 3.4 nM. GSK1120212 demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, GSK1120212 does not show drastic inhibitory activity against the other 98 kinases. GSK1120212 displays potent inhibitory activity against human colorectal cancer cell lines. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, are most sensitive to GSK1120212 with IC50 0.48 nM and 0.52 nM, respectively. The cell lines bearing a K-Ras mutation show a wide range of sensitivity to GSK1120212 with IC50 of 2.2-174 nM. In contrast, COLO320 DM cells, bearing the wild-type gene in both B-Raf and K-Ras, are found to be resistant to GSK1120212 even at 10 μM. GSK1120212 treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, GSK1120212 treatment leads to upregulation of p15INK4b and/or p27KIP1 in most of the colorectal cancer cell lines. GSK1120212 inhibits constitutive ERK phosphorylation in all sensitive cell lines. GSK1120212 induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive to GSK1120212 than HT-29 cells in terms of apoptosis induction. GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).

• 体内研究：
  Oral administration of GSK1120212 at 0.3 mg/kg or 1 mg/kg once daily for 14 days is effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of GSK1120212 almost completely blocks the tumor increase. The phosphorylation of ERK1/2 is completely inhibited in the established tumor tissues by single oral dose of 1 mg/kg GSK1120212, and both p15INK4b and p27KIP1 protein levels are upregulated after 14 days of treatment with GSK1120212. In the COLO205 xenograft model, tumor regression is observed even at a dose of 0.3 mg/kg. At a dose of 1 mg/kg, a complete regression is obtained in 4 out of 6 mice in which the tumor degenerates to the point that tumor volume is not measurable.Administration of GSK1120212 at 0.1 mg/kg almost completely suppresses adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively

• 细胞实验： Cell lines: HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320 cells Concentrations: ~10 μM Incubation Time: 3 or 4 days Method: Exponentially growing cells are precultured in 96-well tissue culture plates for 24 hours and then exposed to GSK1120212. Cell growth is determined by an in vitro toxicology assay kit, sulforhodamine B based. For apoptosis assay, both floating and adherent cells are collected and fixed with 70% ethanol. After washing with PBS, the cells are suspended in 100 μg/mL RNase and 25 μg/mL propidium iodide (PI) and incubated at 37 °C for 30 minutes in the dark. The DNA content of each single cell is determined using the flow cytometer Cytomics FC500 or Guava EasyCyte plus.

• 动物实验： Animal Models: Female BALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells Dosages: ~1 mg/kg/day Administration: o.g.

• 参考文献：
  1. Takayuki Yamaguchi, 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. 2011 Jul;39(1):23-31. 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. 2012 May;61(5):445-54.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.442 ml	7.21 ml	14.419 ml
  5 mM	0.288 ml	1.442 ml	2.884 ml
  10 mM	0.144 ml	0.721 ml	1.442 ml
  50 mM	0.029 ml	0.144 ml	0.288 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

• 1. [IF=2.649] Xianhao Su et al."Preparation and Characterization of a Novel Triple Composite Scaffold Containing Silk Fiborin, Chitosan, and Alginate for 3D Culture of Colonic Carcinoma Cells In Vitro."Med Sci Monitor. 2020; 26: e922935-1–e922935-17

输入产品批号：

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *