Open-source chemoinformatics platforms for multi-target structure-activity relationships

Abstract

Structure-activity relationships (SARs) are fundamental in medicinal chemistry, linking chemical structure with biological activity. However, many diseases involve multiple targets and pathways, making polypharmacology a key consideration. Traditional SAR approaches consider one target at a time, but the scale and complexity of modern screening data demand integrative methods. Chemoinformatic methods have been adapted to mine structure-multiple activity relationships (SMARTs) from large multi-target datasets, enabling analysis of compounds across multiple assays simultaneously. In this review, we map the current "SMART toolbox" of open-source chemoinformatics platforms, highlighting twelve tools that link chemical structures to diverse biological activities and provide integrative data-visualization capabilities. For each platform, we note open-source availability to promote reproducibility. Collectively, these platforms enable integrative visualization and analysis of multi-target activity landscapes, accelerating discovery of multi-functional therapeutics. Finally, we illustrate these approaches in a peptide design case study, showing how SMARTs analysis can guide the engineering of multi-functional bioactive compounds.