IWP-2

Wnt signaling proteins are small secreted proteins that are active in embryonic development, tissue homeostasis, and tumorigenesis.{17947,14336,13185} Wnt proteins bind to receptors on the cell surface, initiating a signaling cascade that leads to ?-catenin activation of gene transcription. IWP-2 is an inhibitor of Wnt production that impairs Wnt pathway activity in vitro with an IC50 value of 27 nM.{17505} IWP-2 inactivates Porcupine, a membrane-bound O-acyltransferase responsible for palmitoylating Wnt proteins, which is essential for their signaling ability and secretion.{17505} At 5 ?M, IWP-2 has been shown to block Wnt-dependent phosphorylation of the frizzled co-receptor and the scaffold protein Dishevelled, preventing the accumulation of ?-catenin.{17505} This compound has been used to suppress embryonic stem cell self-renewal and to decrease cancer cell proliferation, migration, and invasion.{23268,23269}