OM-153

OM-153 is a potent and selective small-molecule inhibitor of tankyrase 1 and 2 (TNKS1/2). By inhibiting the poly-ADP-ribosylation of AXIN proteins, OM-153 prevents their degradation by the ubiquitin-proteasomal system, thereby stabilizing the β-catenin degradosome and suppressing oncogenic WNT/β-catenin signaling. Developed through a collaboration involving Oslo University Hospital, the University of Oslo, and Symeres, OM-153 is a 1,2,4-triazole-based compound designed with improved ADME and pharmacokinetic properties to overcome the intestinal toxicity typically associated with tankyrase inhibition. Preclinical studies have demonstrated its efficacy in colon cancer xenografts and synergistic anti-tumor effects when combined with anti-PD-1 therapy in melanoma models, maintaining a therapeutic index above 10 in mouse studies.