IWP-4

IWP-4 is a potent inhibitor of Wnt production that blocks Wnt pathway activity in vitro (IC₅₀ = 25 nM). IWP-4 inactivates Porcupine (porcn), 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. IWP-4 has been used to induce cardiomyocyte differentiation from human pluripotent stem cells.