Trametinib (GSK1120212), 双特异性丝裂原活化蛋白激酶激酶；MEK1/2 抑制剂

小分子

曲美替尼（GSK1120212）

JTP-74057, Mekinist

Trametinib (GSK1120212)

T407821-1ml

1ml

Moligand™

10mM in DMSO

-80℃储存

超低温冰袋运输

Trametinib (GSK1120212)是一种高特异性的，有效的MEK1/2抑制剂，IC50为0.92 nM/1.8 nM，对c-Raf， B-Raf， ERK1/2没有抑制活性。An allosteric inhibitor of MEK1/MEK2. Information In vitro 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 p15 INK4b and/or p27 KIP1 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). In vivo 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 p15 INK4b and p27 KIP1 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. Cell Data cell lines： Concentrations： Dissolved in DMSO, final concentrations ~10 μM Incubation Time： 3 or 4 days Powder Purity:≥98%

曲美替尼（GSK1120212、JTP-74057、Mekinist）是一种高度特异性的强效 MEK1/2 抑制剂，在无细胞实验中的 IC50 为 0.92 nM/1.8 nM，对 c-Raf、B-Raf、ERK1/2 的激酶活性无抑制作用。曲美替尼可激活自噬并诱导细胞凋亡。

871700-17-3(DMSO)

C26H23FIN5O4

615.39 g/mol

CN1C(=O)C(=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC4=CC=C(I)C=C4F)C5=CC(=CC=C5)NC(C)=O)C

Solubility (25°C) In vitro DMSO: 48 mg/mL (198.12 mM); Ethanol: 48 mg/mL (198.12 mM); Water: Insoluble;

抑制剂

双特异性丝裂原活化蛋白激酶激酶；MEK1/2 抑制剂