Uses
IWP-2-V2 is a IWP-2 (HY-13912) analogue that retains activity against the Wnt/β-catenin pathway[1].
Biological Activity
iwp-2-v2 is a wnt production inhibitor.wnt signaling proteins are small secreted proteins that are active in tissue homeostasis, embryonic development, and tumorigenesis. wnt proteins bind to receptors, initiating a signaling cascade that results in β-catenin activation of gene transcription.
in vitro
iwp-2 was identified as an inhibitor of wnt production inactivating porcupine, a membrane-bound o-acyltransferase whose palmitoylation activity was essential for the signaling ability and secretion of wnt proteins. iwp-2-v2 is a less potent iwp-2 derivative whose chemical structure retains the benzothiazole group of its parent compound. iwp-2-v2 was used to evaluate which structural features of iwp-2 were critical for impairing wnt/β-catenin pathway activity [1].
in vivo
in cci rats, repetitive i.t. administration of iwp-2 (20 μm) in the early phase could significantly delay production of mechanical allodynia. the same drug administrated in the late phase produced long-lasting inhibitory effects on the established mechanical allodynia. such analgesia lasted 4–6 days for iwp-2 after termination of the third treatment. these results showed similar inhibitory effects of iwp-2 on thermal hyperalgesia after cci treatment [2].
References
[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] y. zhang et al. wnt signaling underlies the pathogenesis of neuropathic pain in rodents. j clin invest. 2013 may 1; 123(5): 2268–2286.
