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Overview
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Background
IC50: 40 nMIWP-3 is an inhibitor of Wnt production.Wnt signaling proteins, a group of small secreted proteins, are active in tissue homeostasis, embryonic development, as well as tumorigenesis. Wnt proteins can bind to the cell surface receptors, initiating a signaling cascade that results in the β-catenin activation of gene transcription. In vitro: In previous study, IWP-3 was identified as an inhibitor of Wnt production that could regulate in vitro Wnt pathway activity with an IC50 value of 40 nM. In addition, IWP-3 was found to be able to inactivate porcupine, a O-acyltransferase for palmitoylating Wnt proteins that was critical for the signaling ability and secretion. Moreover, IWP-3 at 5 μM was found to block Wnt-dependent phosphorylation of the low-density lipoprotein receptor-related protein 6 and the scaffold protein Dishevelled, resulting in preventing the accumulation of β-catenin [1]. In another study, IWP-3 was applied to promote cardiomyocyte generation from human embryonic stem cells by inhibiting Wnt signaling [2].In vivo: So far, there is no animal in vivo data reported. Clinical trial: Up to now, IWP-3 is still in the preclinical development stage.
[1] B. Chen, M. E. Dodge, W. Tang, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nature Chemical Biology 5(2), 100-107 (2009).
[2] E. Willems, S. Spiering, H. Davidovics, et al. Small molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell derived mesoderm. Circulation Research 109(4), 360-364 (2011).
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