XAV939

XAV939 is a small-molecule inhibitor that targets the tankyrase enzymes TNKS1 and TNKS2 (poly ADP-ribose polymerases 5 and 6). It was described as a selective antagonist of canonical Wnt signaling and has been widely used as a pharmacological tool in cell biology to study Wnt pathway regulation. As a research reagent, XAV939 is available from various suppliers for in vitro experiments.

Mechanism of action

XAV939 binds to the catalytic PARP domain of tankyrases and inhibits their PARsylation activity. This inhibition prevents the degradation of AXIN proteins, leading to stabilization of AXIN1 and AXIN2. The increased AXIN levels promote β-catenin degradation, resulting in reduced transcriptional activity of Wnt/β-catenin target genes.

Experimental use and considerations

In cell culture and organoid models, XAV939 is used to dampen canonical Wnt signaling. Effective concentrations typically fall in the low micromolar range, and experiments may span from several hours to days depending on the system and readouts. It is frequently contrasted with other tankyrase inhibitors such as IWR-1 and G007-LK. Researchers use XAV939 to dissect Wnt-dependent processes in development, stem cell maintenance, and cancer models. While valuable, its effects can vary by cell type, and off-target effects or tankyrase-related functions beyond Wnt signaling can complicate interpretation.

Limitations and safety

XAV939 is intended for research use and is not approved for clinical applications. Tankyrases have multiple cellular roles, including telomere maintenance, so the compound may produce effects beyond Wnt pathway modulation. In vivo applicability is limited by pharmacokinetic and bioavailability considerations, and results observed in vitro may not always translate to whole organisms.

Availability

XAV939 is commercially available from multiple suppliers for in vitro research use. Related tankyrase inhibitors are used in parallel studies to compare mechanisms and outcomes.