Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

The high frequency of activating RAS or BRAF mutations in cancer provides strong rationale for targeting the MAPK pathway. Selective BRAF and MEK inhibitors have shown clinical efficacy in melanoma patients. However, the majority of responses are transient and resistance is often associated with pathway reactivation of the ERK signaling pathway. Here we describe the identification and characterization of SCH772984, a novel and selective inhibitor of ERK1/2 which displays behaviors of both type I and type II kinase inhibitors…”


New Drug Overcomes Resistance to BRAF Inhibitors in Mice and Cultured Human Cells

An experimental drug may strengthen treatments that target melanomas with mutations in the BRAF gene, reported researchers from the pharmaceutical company Merck at the American Association for Cancer Research’s 2013 meeting. Treatments that target BRAF often stop working because tumors activate a related protein called ERK, which is the target of Merck’s new drug. Called SCH772984, the drug inhibits ERK in cultured human tumor cells with BRAF, NRAS, or KRAS mutations; slows cell division in human tumor cells that resist treatments that target BRAF or MEK; and shrinks tumors in mice. The researchers have begun a phase I clinical trial of an ERK inhibitor in people with tumors.


Preclinical Study Indicates Potential for Novel Inhibitor to Overcome Drug Resistance Induced by RAF, MEK Inhibitors

WASHINGTON, D.C. — A new class of investigational medicines may help to treat patients with cancers driven by mutations in genes such as BRAF or KRAS/NRAS, including those patients who have become resistant to therapies that target BRAF directly,…