WIKI4

WIKI4 is a potent and selective small molecule inhibitor of the Wnt/β-catenin signaling pathway. It functions by inhibiting the enzymatic activity of tankyrase 1 and 2 (TNKS1/2), which are members of the poly(ADP-ribose) polymerase (PARP) family. By inhibiting tankyrase, WIKI4 prevents the PARsylation-mediated ubiquitylation and subsequent proteasomal degradation of AXIN, a rate-limiting component of the β-catenin destruction complex. This stabilization of AXIN leads to increased degradation of cytoplasmic β-catenin, thereby suppressing the transcription of Wnt-responsive genes. WIKI4 is widely utilized as a chemical probe in research to investigate the role of Wnt signaling in oncology, regenerative medicine, and developmental biology. Structurally, it binds to the adenosine subsite of the donor NAD+ binding groove of the tankyrase catalytic domain.