LGK974 inhibits PORCN

Aberrant WNT signaling is associated with the development of numerous cancers, and strategies for targeting this pathway are under intense investigation (reviewed in Polakis, 2012; Polakis, 2000; Yao et al, 2011). Secretion of WNT ligand depends on its PORCN-dependent palmitoleoylation in the ER, making PORCN a attractive therapeutic target in cases where WNT is aberrantly over-expressed (reviewed in MacDonald et al, 2009). LGK974 is a PORCN-inhibitor that was identified in a screen for compounds that abrogate the secretion of WNT ligands, and is in Phase I clinical trials for the treatment of WNT-dependent cancers

Summary from Reactome (R-HSA-5340573), read 2026-09-23.