IC50: 27 nM for Wnt pathway activity
The Wnt signaling pathway is important in embryonic development as well as the initiation and progression of a number of types of human cancer. Porcn, a member of the membrane-bound O-acyltransferase (MBOAT) family, adds a palmitoyl group to Wnt proteins that is essential to their signaling ability and is required for Wnt secretion. IWP-2 is a small-molecule antagonist of the Wnt/b-catenin pathway.
In vitro: Expression of Porcn but not Evi alleviated the effects of IWP-2 on pathway activity and Wnt secretion, which suggests that in general IWP-2 may act on Porcn .
In vivo: In order to test the in vivo activity of IWP-2, the authors turned to a simple and rapid assay of Wnt/b-catenin pathway activity: regeneration of the zebrafish caudal fin following resection. The addition of IWP-2 to the aquarium water of zebrafish failed to suppress fin regeneration after mechanical resection, which suggests either that IWP-2 have poor bioavailability or that the determinants in the gene product that they target are not conserved in zebrafish .
Clinical trial: Up to now, IWP-2 is still in the preclinical development stage.
 Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7.