XAV939 selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM, regulates axin levels and does not affect CRE, NF-κB or TGF-β.

The Wnt signaling pathway is integral to normal biological processes and inappropriately active in many cancers. It is regulated through degradation of the downstream effector β-catenin via a complex consisting of the tumor suppressor APC, axin, and glycogen synthase kinase 3 (GSK3). Axin is the concentration-limiting factor for this degradation complex. Initially indentified as telomere-associated proteins, tankyrases promote axin ubiquitination, possibly through poly-ADP-ribosylation (PARsylation).XAV939 is a potent, small molecule inhibitor of tankyrase (TNKS) 1 and 2 with IC50 values of 11 and 4 nM, respectively.By inhibiting TNKS activity, XAV939 increases the protein levels of the axin-GSK3β complex and promotes the degradation of β-catenin in SW480 cells.At concentrations as low as 0.33 µM, XAV939 inhibits colony formation of APC-deficient colorectal cancer cells.

BIO

WIKI4

A-966492

AG14361

AZD-2461