Cobimetinib 是一种可口服的MEK1选择性抑制剂，抑制MEK1的IC50为4.2 nM。

Cobimetinib is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) (IC50: 0.9 nM). Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation.

在负荷KRAS和BRAFV600E突变型肿瘤的小鼠体内,Cobimetinib (10 mg/kg, p.o.)对肿瘤病程有抑制作用.[1]在负荷耐药的A375异种移植物小鼠体内,Cobimetinib与GDC-0941联用还可减少己糖激酶II,Ksr,c-RAF 和p-MEK蛋白质的水平.

Cobimetinib对多种肿瘤细胞生长均有强烈的抑制作用,尤其是KRAS或BRAF突变型癌细胞系。Cobimetinib与GDC-0941联用可降低888MEL和A2058细胞的生存能力,并抑制通路、增加细胞凋亡。[1]Cobimetinib和vemurafenib联用可使所有BRAFV600E系中细胞膜上的GLUT-1减少程度显著加剧。

Cells are plated in quadruplicate at a density of 3,000 per well in 384-well plates in normal growth medium and allowed to adhere overnight. Compounds are added in 10 concentrations based on a 3-fold dilution series. Cell viability is measured 72 h later using the CellTiter-Glo Luminescent Cell Viability Assay.(Only for Reference)

934660-93-2

C21H21F3IN3O2

531.318

考比替尼;可美替尼;GDC-0973;RG7420;XL518

Ethanol:44 mg/mL (82.8 mM)
DMSO:93 mg/mL (175 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years