Trametinib

A potent and highly specific MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM; exhibits no inhibition on the kinase activities of c-Raf, B-Raf, ERK1/2.Skin Cancer Approved (In Vitro) :Trametinib (GSK1120212; JTP-74057) (0.1-100 nM) blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs) . Trametinib (JTP-74057) inhibits the growth of 9 out of 10 human colorectal cancer cell lines, and they shows cell-cycle arrest at the G1 phase after drug tratment.The combination of GSK2118436 and Trametinib (GSK1120212) effectively inhibits cell growth, decreases ERK phosphorylation, decreases cyclin D1 protein, and increases p27 (kip1) protein in the resistant clones. (In Vivo) :Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (GSK1120212; JTP-74057) or 10 mg/kg of HWA486.Trametinib (0.3 mg/kg, 1 mg/kg, p.o.) is effective in inhibiting the HT-29 xenograft growth in a nude mouse xenograft model.