印度Trametinib

产品描述

Trametinib is an ATP-noncompetitive inhibitor of MEK 1/2 (IC50s: 0.7/0.9 nM). It shows low inhibition for more than 180 kinases, including B-Raf, c-Raf, and MEK5.

靶点活性

MEK1,0.92nM

MEK2,1.8nM

实验溶液

30% PEG400+0.5% Tween80+5% propylene glycol: 15 mg/mL

体外活性

Trametinib (JTP-74057) inhibited the phosphorylation of MBP regardless of the isotype of Raf and MEK (IC50s: 0.92 to 3.4 nM). JTP-74057 demonstrated no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, were most sensitive to JTP-74057, showing subnanomolar IC50 values. The cell lines bearing a K-Ras mutation showed a wide range of sensitivity to JTP-74057 [1]. Among KRAS mutant cell lines, cell lines with an expression pattern suggestive of epithelial-to-mesenchymal transition were less sensitive to GSK1120212. A proportion of cell lines from certain tissue types not known to carry frequent RAF/RAS mutations also seemed to be sensitive to GSK1120212 [2].

体内活性

Both 0.3 mg/kg and 1 mg/kg of JTP-74057 were effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of JTP-74057 blocked the tumor increase almost completely. Neither significant changes in body weight nor gross lesions at autopsy were observed in the mice treated with 1 mg/kg of JTP-74057. The phosphorylation of ERK1/2 was completely inhibited in the established tumor tissues by a single oral dose of 1 mg/kg JTP-74057, and both p15INK4b and p27KIP1 protein levels were upregulated after 14 days of treatment with JTP-74057 [1]. JTP-74057 blocked tumor necrosis factor-α and interleukin-6 production from PBMCs. AIA and CIA development were suppressed almost completely by 0.1 mg/kg of JTP-74057. In the CIA, JTP-74057 suppressed collagen-reactive T-cell proliferation ex vivo [3].

激酶实验

Raf-MEK-ERK cascade kinase assay: Non-phosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is mixed with unphosphorylated MEK1/MEK2 and ERERK2 in 10 μM ATP and 12.5 mM MgCl2 containing MOPS buffer in the presence of various concentrations of GSK1120212. The phosphorylation of MBP is detected by the anti-phospho-MBP antibody.

细胞实验

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.(Only for Reference)

细胞系： HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320

动物实验

动物模型：FeBALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells

分子量

615.39

分子式

C26H23FIN5O4

CAS

871700-17-3

溶解度

DMSO: 21 mg/mL (34.1 mM)

Ethanol: <1 mg/mL

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.