Data-driven strategies for drug repurposing: insights, recommendations, and case studies

Abstract

Drug discovery is a complex, time-intensive, and costly process, often requiring more than a decade and substantial financial investment to bring a single therapeutic to market. Drug repurposing, the systematic identification of new indications for existing approved drugs, offers a cost-effective and expedited alternative to traditional pipelines, with the potential to address unmet clinical needs. In this study, we present a comparative analysis of drug–target interaction data from three extensively curated resources: ChEMBL, BindingDB, and GtoPdb, evaluating their release histories, curation methodologies, and coverage of approved and investigational compounds and targets. To facilitate therapeutic interpretation, we manually classified ChEMBL targets into 12 high-level biological families and mapped 817 clinically approved drug indications into 28 broader therapeutic groups. This structured framework enabled a systematic profiling of physicochemical properties among approved drugs across therapeutic categories. Our analyses revealed associations between physicochemical characteristics and therapeutic groups, providing practical guidance for indication-specific compound prioritization and refining the repurposing studies. We also examined cross-indication drug approvals to identify areas with high repurposing potential. Finally, we implemented a pathway-based computational pipeline to predict repositioning opportunities for FDA-approved drugs across 10 major cancer types, demonstrating its adaptability to other disease contexts. Overall, this work consolidates drug-target data and computational repurposing into a data-driven framework that advances drug discovery and translational applications.