Ulixertinib

Ulixertinib (developmental code BVD-523) is an investigational small-molecule inhibitor of extracellular signal–regulated kinases 1 and 2 (ERK1/2). It is an orally available, ATP-competitive kinase inhibitor designed to target the terminal kinases of the RAS–RAF–MEK–ERK pathway, a signaling cascade frequently dysregulated in cancer. By inhibiting ERK1/2, ulixertinib aims to suppress proliferation and survival signals in tumor cells, and to overcome or prevent resistance that can arise with upstream RAF or MEK inhibitors.

Preclinical studies showed biochemical selectivity for ERK1/2 and antiproliferative activity across models with activating mutations in BRAF, RAS, or other components of the MAPK pathway. Clinical development has focused on phase I and II trials in patients with advanced solid tumors, including BRAF‑mutant melanoma and other MAPK‑altered cancers. Early clinical data reported objective responses in a subset of patients, including those with BRAF V600 mutations, and indicated potential activity in tumors that progressed on prior RAF or MEK inhibition.

Common adverse events observed in trials include diarrhea, fatigue, nausea, rash, and transient liver enzyme elevations; dose‑limiting toxicities and tolerability have guided dose selection in studies. As of the last update, ulixertinib remains an investigational agent and is not approved for routine clinical use. Ongoing research seeks to better define responsive tumor types, optimal combination strategies, and biomarkers predictive of benefit.