MedKoo product information:

  GDC-0973

MEK inhibitor GDC-0973 is an orally bioavailable small-molecule inhibitor of mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), with potential antineoplastic activity. MEK inhibitor GDC-0973 specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a B-RAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

GDC-0973 is a potent and highly selective inhibitor of MEK (Figure 1A), with a biochemical IC50 of 4.2 nM against MEK1. In biochemical assays, GDC-0973 demonstrated >100-fold selectivity for MEK when tested against a panel of >100 serine-threonine and tyrosine kinases. GDC-0973 shows strong cellular potency in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines

Current developer:   Genentech

1: Hoeflich KP, Merchant M, Orr C, Chan J, Den Otter D, Berry L, Kasman I, Koeppen H, Rice K, Yang NY, Engst S, Johnston S, Friedman LS, Belvin M. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2011 Nov 16. [Epub ahead of print] PubMed PMID: 22084396.