In silico screening study for the identification of potential tankyrase 1 inhibitors against ovarian cancer

Abstract

Ovarian cancer remains one of the leading causes of cancer-related mortality among women, highlighting the need for developing effective therapeutic strategies. The tankyrase 1 (TNKS1), a key regulator of Wnt/β-catenin signaling pathway, presents itself as a potential target in treatment of cancer. In this study, a multi-stage in silico approach involving several steps was used to find potential TNKS1 inhibitors out of 6,000 DrugBank compounds. Following molecular docking, the top candidates were further filtered through binding interaction analysis with critical active-site residues and ADMET evaluation. Among 34 compounds, Ligand 16752640 is identified as the best candidate for having the most favorable pharmacokinetic and toxicity profile, showing the lowest predicted toxicity, minimal blood-brain barrier permeability, having the least plasma clearance, weak CYP inhibition, hERG inhibition and the best drug-likeness based on Lipinski's rule of five. Ligand 449087 and Tasosartan (60919) also showed promising characteristics. Overall, the identified lead compounds represent promising candidates for TNKS1-targeted therapy and provide a foundation for future experimental validation and potential drug repurposing in ovarian cancer treatment.