JW55

JW55 is a small molecule inhibitor of tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) that acts as a potent antagonist of the canonical Wnt/β-catenin signaling pathway. Discovered through high-throughput screening by researchers at Oslo University Hospital and the University of Oslo, JW55 binds to the adenosine pocket of the catalytic PARP domain of TNKS1/2. This inhibition prevents the poly(ADP-ribosyl)ation (PARsylation) and subsequent proteasomal degradation of AXIN2, a key scaffold protein of the β-catenin destruction complex. Consequently, stabilized AXIN2 promotes the phosphorylation and degradation of β-catenin, suppressing Wnt-mediated transcription. Preclinically, JW55 has demonstrated efficacy in reducing cell proliferation, colony formation, and tumor growth in colorectal cancer models (particularly those with APC mutations), as well as showing potential in triple-negative breast cancer, osteosarcoma, and obesity-related intestinal hyperplasia.

Other names

N-[4-[[[[tetrahydro-4-(4-methoxyphenyl)-2H-pyran-4-yl]methyl]amino]carbonyl]phenyl]-2-furancarboxamideTankyrase 1/2 Inhibitor IV