TNKS-2-IN-3

TNKS-2-IN-3 (Compound 5) is a selective and competitive inhibitor of Tankyrase 2 (TNKS2), with an IC50 value of 0.3 nM. It exhibits over 20-fold selectivity for TNKS2 compared to TNKS1 and more than 100-fold selectivity over PARP1/2. By inhibiting TNKS2-mediated ADP ribosylation, TNKS-2-IN-3 stabilizes axin and suppresses the Wnt/β-catenin pathway, demonstrating antiproliferative activity in colorectal cancer cells. TNKS-2-IN-3 holds potential for research in solid tumors with aberrant Wnt pathway activation, such as colorectal cancer.