LGK 974 is a potent and specific small molecule Porcupine (PORCN) inhibitor. Porcupine (PORCN) is a membrane bound O-acyltransferase that mediates palmitoylation of Wnt family proteins. This step is required for secretion and biologic activity of Wnt proteins, which have roles in embryonic development and cancer. LGK 974 greatly reduces Wnt secretion without decreasing its synthesis and without increasing cytotoxicity. LGK 974 is orally bioavailable in mice and induces tumor regression in mouse breast tumors produced by mammary tumor virus-driven Wnt1 signaling. Interestingly, it can also block carcinogenesis in other Wnt-related tumors at doses that have limited impact on stem cell renewal.