ETC-535

ETC-535 is a small molecule inhibitor of Porcupine (PORCN), a multi-pass membrane-bound O-acyltransferase (MBOAT) located in the endoplasmic reticulum that is essential for the post-translational palmitoylation and secretion of Wnt ligands. Developed by the Experimental Therapeutics Centre (ETC) in Singapore in collaboration with Duke-NUS Medical School, ETC-535 targets the Wnt-beta-catenin signaling pathway, which is frequently dysregulated in various cancers. In preclinical studies, ETC-535 demonstrated significant antitumor efficacy and favorable oral pharmacokinetic properties in mouse models of Wnt-driven cancers, including orthotopic breast cancer (MMTV-Wnt1) and pancreatic ductal adenocarcinoma (HPAF-II). However, a sibling compound, ETC-159, was ultimately selected as the lead candidate for clinical development.