[CAS NO. 1184173-73-6]  MK-8353 (SCH900353)

MK-8353 is a potent and selective inhibitor of both active and inactive ERK1 and ERK2 kinases (IC50=20 and 7 nM, respectively). MK-8353 is not a potent inhibitor of human CYPs 1A2, 2C9, 2C19 or 2D6 but inhibits CYP 3A4 (pre-incubation) in vitro and shows inhibition of CYP 3A4 and 2C8 (IC50 = 1.7 & 3.5 μM), which can cause drug-drug interactions when co administered with drugs that are primarily metabolized by CYP 2C8 or 3A4. MK-8353 is a weak inhibitor of hERG current, producing 16% inhibition at 0.6 μM. The IC50 values for inhibiting cell prolifertion are 371, 51, and 23 nM in A2058, HT-29, and Colo-205 cells respectively. In addition to inhibiting the kinase activity of ERK, MK-8353 prevents the phosphorylation of ERK by MEK. MK-8353 demonstrates kinase selectivity over a 227-human kinase panel; no additional kinase in the panel is inhibited by more than 35% at the 0.1 μM concentration, and only 3 kinases (CLK2, FLT4, and Aurora B) are inhibited >50% at the 1.0 μM concentration.