MK-8353 (SCH-900353) is a highly potent, orally bioavailable, dual-specificity ERK1/2 inhibitor with IC50 of 23.0/8.8 nM, respectively.
MK-8353 inhibits nonactivated ERK2 with IC50 of 0.5 nM, demonstrates excellent kinase selectivity over a 227-human kinase panel.
MK-8353 decreases pERK1, pERK2, and ribosomal S6 kinase (pRSK) proteins, with complete suppression of pERK1 and pERK2 observed at 30 nM in A2058 cells.
MK-8353 inhibits the in vitro proliferation of a panel of BRAFV600-mutant and RAS-mutant cancer cell lines.
MK-8353 exhibits in vivo antitumor activity against BRAFV600 mutant Colo-205 colon cancer model and the BRAFV600 mutant SK-MEL-28 melanoma model.
