Refametinib

Refametinib is an inhibitor of both mitogen-activated protein kinase kinases 1 (MEK1) and 2 (MEK2) with IC₅₀ values of 19 and 47 nM respectively. It binds in an allosteric site adjacent to the ATP pocket and is selective for MEK1/2 versus 205 other kinases (Iverson et al.).

CANCER RESEARCH

• Inhibits growth of cancer cell lines in vitro, including those expressing B-RAF mutation V600E (Iverson et al.).
• Inhibits tumor growth in various xenograft models including human melanoma A375 and human colon cancer Colo205 cell lines, and primary pancreatic cancers (Iverson et al.; Chang et al.).
• Synergistically induces apoptosis in pancreatic cancer cell lines when combined with Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor (Diep et al.).
• Synergistically inhibits tumor growth in hepatocellular carcinoma rodent models when combined with Sorafenib, an inhibitor of the tyrosine kinases vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR; Schmieder et al.).