Trametinib, Inhibitor

Trametinib (GSK1120212)

Cat. Num. AAA576333

• Purity: 99.72%
• Synonyms: Trametinib; Trametinib (GSK1120212); inhibitor

• Purity/Purification: 99.72%
• Form/Format: POWDER

• CAS Number: 871700-17-3
• Molecular Formula: C26H23FIN5O4
• Solubility: DMSO: 21 mg/mL (34.1 mM); Ethanol: <1 mg/mL; ( < 1 mg/ml refers to the product slightly soluble or insoluble )
• Receptor (IC50): MEK1: 0.92nM; MEK2: 1.8nM
• Apprearence: Solid
• Analytical Data: HNMR: Consistent with structure; HPLC: Consistent with structure
• Conclusion: The test results consistent with structure
• In vitro Activity: 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].
• In vivo Activity: Both 0.3 mg/kg and 1 mg/kg of JTP-74057 were effective in inhibiting the HT-29 xenograft growth, and 1mg/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-? 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].
• Kinase Assay: 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 uM 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.
• Cell Assay: 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 ?g/mL RNase and 25 ?g/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); Cell line: HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320
• Animal Experiment: Animal Model: FeBALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells
• Preparation and Storage: 2 years -80°C in solvent; 3 years -20°C powder

Structure

Related Product Information for Trametinib, inhibitor

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.