ETC-159

ETC-159 is a selective small molecule inhibitor of porcupine (PORCN), an enzyme required for palmitoylation and secretion of all Wnt ligands. It inhibits β-catenin reporter activity (IC50 = 2.9 nM) and reduces the interaction of Wnt with its carrier protein WLS via decreased Wnt palmitoylation in STF3A cells, an effect that is reversed by overexpression of recombinant PORCN. In preclinical studies, ETC-159 induces tumor regression in patient-derived xenograft models.