JW 55

Description: JW 55 is a potent and selective small molecule inhibitor of beta-catenin signaling pathway, it functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2) which are regulators of the beta-catenin destruction complex. JW 55 decreases auto-PARsylation of TNKS1/2 in vitro with IC50s of 1.9 uM and 830 nM respectively. Inhibition of TNKS1/2 poly(ADP-ribosyl)ation activity by JW55 led to stabilization of AXIN2, a member of the beta-catenin destruction complex, followed by increased degradation of beta-catenin. JW55 inhibited canonical Wnt signaling in a dose-dependent manner in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of beta-catenin. In addition, JW55 reduced XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice.

References: Cancer Res. 2012 Jun 1; 72(11):2822-32.