Cayman IWP-3

Wnt signaling proteins are small secreted proteins that are active in embryonic development, tissue homeostasis, and tumorigenesis.^1,2,3 Wnt proteins bind to receptors on the cell surface, initiating a signaling cascade that leads to β-catenin activation of gene transcription. IWP-3 is an inhibitor of Wnt production that impairs Wnt pathway activity in vitro with an IC₅₀ value of 40 nM.⁴ IWP-3 inactivates porcupine, a membrane-bound O-acyltransferase responsible for palmitoylating Wnt proteins, which is essential for their signaling ability and secretion.⁴ At 5 μM, IWP-3 has been shown to block Wnt-dependent phosphorylation of the low-density lipoprotein receptor-related protein 6 (LRP6) and the scaffold protein Dishevelled, preventing the accumulation of β-catenin.⁴ By inhibiting Wnt signaling, IWP-3 has been used to promote cardiomyocyte generation from human embryonic stem cells (EC₅₀ = 1.2 μM).⁵

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