Tankyrases (TNKS) are poly(ADP-ribose) polymerases (PARPs) that cleave NAD+ to produce nicotinamide and ADP-ribose, which is then covalently attached to an acceptor protein in a process known as poly(ADP-ribosyl)ation. TNKS have key roles in the Wnt signaling pathway as part of the β-catenin destruction complex. JW 74 is an inhibitor of the catalytic PARP domain of TNKS1/2 that blocks canonical Wnt signaling with an IC50 value of 790 nM. It increases the levels of Axin2 and decreases β-catenin levels in colorectal cancer (CRC) cells, leading to down-regulation of Wnt target genes. JW 74 inhibits the growth of CRC xenograft tumors in mice. JW 74 induces apoptosis and differentiation in osteosarcoma cell lines.
