Background: Tankyrases are known for their multifunctionalities within the poly(ADPribose) polymerases
family and playing vital roles in various cellular processes which include the regulation of tumour
suppressors. Tankyrases, which exist in two isoforms; Tankyrase 1 and 2, are highly homologous and an integral
part of the Wnt β-catenin pathway that becomes overly dysregulated when hijacked by pro-carcinogenic
Methods: In this review, we cover the distinct roles of the Tankyrase isoforms and their involvement in the
disease pathogenesis. Also, we provide updates on experimentally and computationally derived antagonists of
Tankyrase whilst highlighting the precedence of integrative computer-aided drug design methods towards the
discovery of selective inhibitors.
Results: Despite the high prospects embedded in the therapeutic targeting and blockade of Tankyrase isoforms,
the inability of small molecule inhibitors to achieve selective targeting has remained a major setback, even until
date. This explains numerous incessant drug design efforts geared towards the development of highly selective
inhibitors of the respective Tankyrase isoforms since they mediate distinct aberrancies in disease progression.
Therefore, considering the setbacks of conventional drug design methods, can computer-aided approaches actually
save the day?
Conclusion: The implementation of computer-aided drug design techniques in Tankyrase research could help
complement experimental methods and facilitate ligand/structure-based design and discovery of small molecule
inhibitors with enhanced selectivity.