Understanding Tankyrase Inhibitors and Their Role in the Management of Different Cancer

Cancer manifests as uncontrolled cell proliferation. Tankyrase, a poly(ADP-ribose) polymerase member, is vital in Wnt signal transmission, making it a promising cancer therapy target. The Wnt/β-catenin pathway regulates critical biological processes like genomic stability, gene expression, energy utilization, and apoptosis. Its dysregulation contributes to cancer development. Targeting tankyrase within this pathway holds the potential for inhibiting aberrant cell growth and promoting programmed cell death, offering a promising avenue for cancer treatment. ADP-ribosylation, a reversible process, modifies proteins post-synthesis, regulating diverse cellular signaling pathways. Transferase enzymes like mono and poly(ADPribosyl) transferases transfer ADP-ribose from NAD+ to specific amino acid side chains or ADP-ribose units on target proteins. Blocking tankyrase has emerged as a promising strategy in cancer treatment. This article reviews recent advancements in developing novel tankyrase inhibitors. It delves into structure-activity relationships, molecular docking, polypharmacology profiles, and binding mechanisms at the active site. Insights into lead structure development aid in designing potent anti-cancer medications, shedding light on promising avenues in cancer therapy.