LY3214996 is a potent and selective inhibitor of extracellular signal-regulated kinase 2 (ERK2), a key component of the mitogen-activated protein kinase (MAPK) signaling pathway. This pathway is frequently dysregulated in various cancers, especially those with mutations in BRAF or RAS genes. LY3214996 is primarily investigated for its antitumor activity in oncology, particularly in cancers resistant to upstream inhibitors like BRAF or MEK inhibitors. By directly targeting ERK2, it helps overcome resistance mechanisms that reactivate the MAPK pathway downstream of these targets. It has shown promising results in preclinical models of melanoma, colorectal cancer, and non-small cell lung cancer, where sustained ERK inhibition leads to cell cycle arrest and apoptosis. Due to its selectivity and oral bioavailability, LY3214996 is being evaluated in clinical trials for advanced solid tumors, aiming to provide a therapeutic option for patients with limited responses to existing targeted therapies.