The extracellular regulated kinases 1 and 2 (ERK1/2) are functionally redundant kinases activated by a variety of growth factors and mitogens. SCH 772984 is a potent inhibitor of ERK1 and ERK2 (IC50s = 4 and 1 nM, respectively). It is highly selective, with only seven kinases of 300 tested showing more than 50% inhibition at a concentration of 1 μM. SCH 772984 has nanomolar cytotoxicity in tumor cells with mutations in BRAF, NRAS, or KRAS. It is effective in vivo, inducing regression of xenograft tumors in mice. SCH 772984 displays slow binding kinetics, binding to a novel binding pocket in inactive ERK isoforms.
