942183-80-4

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.

SCH772984 is a novel and selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors and has nanomolar cellular potency in tumor cells with mutations in BRAF, NRA5, or KRAS and induces tumor regressions in xenograft models.

ChEBI: SCH772984 is a member of the class of indazoles that is 1H-indazole substituted by pyridin-4-yl and {[(3R)-1-(2-oxo-2-{4-[4-(pyrimidin-2-yl)phenyl]piperazin-1-yl}ethyl)pyrrolidin-3-yl]carbonyl}amino groups at positions 3 and 5, respectively. It is a potent inhibitor of mitogen-activated protein kinases ERK1 and ERK2 (IC50 = 4 and 1 nM, respectively) that exhibits anti-cancer properties. It has a role as an antineoplastic agent, an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, an apoptosis inducer and an analgesic. It is a member of pyridines, a biaryl, a secondary carboxamide, a pyrrolidinecarboxamide, a member of indazoles, a tertiary amino compound, a N-acylpiperazine, a N-arylpiperazine, a member of pyrimidines, a N-alkylpyrrolidine and a tertiary carboxamide.

ERK1

ERK2: 1 nM (IC₅₀); ERK1: 4 nM (IC₅₀)

Store at -20°C

[1] ERICK J MORRIS. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.[J]. Cancer discovery, 2013, 3 7: 742-750. DOI: 10.1158/2159-8290.cd-13-0070
[2] APIRAT CHAIKUAD. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics[J]. Nature chemical biology, 2014, 10 10: 853-860. DOI: 10.1038/nchembio.1629