LGK-974 is a potent and specific inhibitor of Porcupine (porcn), a Wnt-specific acyltransferase (IC₅₀ = ~0.4 nM). GK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. In addition, head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974.