MK-8353 + selumetinib

A combination of two small molecule inhibitors, **MK-8353**, an orally bioavailable dual mechanism inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), and **selumetinib**, an inhibitor of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2). This combination was developed for the treatment of advanced or metastatic solid tumors to target the MAPK pathway at two nodes (ERK and MEK) in hopes of achieving greater pathway inhibition and suppressing drug resistance. Phase 1b studies found this combination to have significant toxicity at higher doses, with most common adverse events being diarrhea, nausea, and dermatological and ocular toxicities. The highest tolerated combination was MK-8353 100 mg plus selumetinib 50 mg, administered orally. However, no objective antitumor responses were seen at tolerable doses.

Other names

MK-8353 + AZD6244