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Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
Published on: September 26, 2025
Exploring compound promiscuity patterns and multi-target activity spaces
Ye Hu1, Disha Gupta-Ostermann1, Jürgen Bajorath2
1Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany ; These authors contributed equally to this work.
Abstract:
Compound promiscuity is rationalized as the specific interaction of a small molecule with multiple biological targets (as opposed to non-specific binding events) and represents the molecular basis of polypharmacology, an emerging theme in drug discovery and chemical biology. This concise review focuses on recent studies that have provided a detailed picture of the degree of promiscuity among different categories of small molecules. In addition, an exemplary computational approach is discussed that is designed to navigate multi-target activity spaces populated with various compounds.
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