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Systematic Analysis of Public Domain Compound Potency Data Identifies Selective Molecular Scaffolds across Druggable Target Families

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journal contribution
posted on 28.01.2010, 00:00 by Ye Hu, Anne Mai Wassermann, Eugen Lounkine, Jürgen Bajorath
Molecular scaffolds that yield target family-selective compounds are of high interest in pharmaceutical research. There continues to be considerable debate in the field as to whether chemotypes with a priori selectivity for given target families and/or targets exist and how they might be identified. What do currently available data tell us? We present a systematic and comprehensive selectivity-centric analysis of public domain target−ligand interactions. More than 200 molecular scaffolds are identified in currently available active compounds that are selective for established target families. A subset of these scaffolds is found to produce compounds with high selectivity for individual targets among closely related ones. These scaffolds are currently underrepresented in approved drugs.