Wnt signaling proteins are small secreted proteins that are active in embryonic development, tissue homeostasis, and tumorigenesis. Wnt proteins bind to receptors on the cell surface, initiating a signaling cascade that leads to β-catenin activation of gene transcription. IWP-2 is an inhibitor of Wnt production (IC50 = 27 nM) that inactivates porcupine, a membrane-bound O-acyltransferase whose palmitoylation activity is essential for the signaling ability and secretion of Wnt proteins. IWP-2-V2 is a less potent IWP-2 derivative whose chemical structure retains the benzothiazole group of its parent compound. It has been used to determine which structural features of IWP-2 are essential for impairing Wnt/β-catenin pathway activity.
