LY3214996

Temuterkib is an orally available inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity. Upon oral administration, temuterkib inhibits both ERK 1 and 2, thereby preventing the activation of mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The MAPK/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.

LY3214996 is an inhibitor of ERK1 and ERK2 (IC50= 5 nM for both). It inhibits cell proliferation of tumor cellsin vitro, including those expressing B-RAF, N-Ras, or K-Ras mutations. LY3214996 inhibits tumor growth in B-RAF or N-Ras mutant melanoma, B-RAF or K-Ras mutant colorectal, lung, and pancreatic cancer mouse xenograft models, as well as patient-derived xenograft (PDX) mouse models.

Temuterkib (LY3214996) is a highly selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays. Temuterkib potently inhibits cellular p-RSK1 in BRAF and RAS mutant cancer cell lines. Temuterkib shows potent antitumor activities in cancer models with MAPK pathway alterations.