cc-90003

CC-90003 is an orally available, irreversible small molecule inhibitor of extracellular signal-regulated kinases 1 and 2 (ERK1/2), key components of the MAPK signaling pathway. It was developed for potential antineoplastic activity, particularly targeting tumors with mutations in RAS or BRAF genes. The drug covalently binds to cysteine residues in the ATP-binding site of ERK1 (Cys183) and ERK2 (Cys164), resulting in potent inhibition with IC50 values between 10–20 nM and high kinase selectivity[1][6][4]. Preclinical studies demonstrated anti-proliferative effects in KRAS-mutant tumor models. In clinical trials, CC-90003 showed significant reduction of free ERK levels but was associated with dose-limiting toxicities including neurotoxicity and peripheral neuropathy, leading to discontinuation of its development for oncology indications[5][9]. The drug was initially developed by Celgene.

Other names

ERK inhibitor (as a synonym in some sources)