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-4 is an inhibitor of Wnt production that impairs Wnt pathway activity in vitro with an IC50 value of 25 nM. IWP-4 inactivates Porcupine, a membrane-bound O-acyltransferase responsible for palmitoylating Wnt proteins, which is essential for their signaling ability and secretion. At 5 μM, IWP-4 has been shown to block Wnt-dependent phosphorylation of the low-density lipoprotein receptor-related protein 6 receptor and the scaffold protein Dishevelled, preventing the accumulation of β-catenin. This compound has been used to induce cardiomyocyte differentiation from human pluripotent stem cells.
