title: Systematic analysis of public domain compound potency data identifies selective molecular scaffolds across druggable target families.
abstract: 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.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universitat, Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.forename: Anne Mai
authors.initials: AM
authors.lastname: Wassermann
authors.forename: Eugen
authors.initials: E
authors.lastname: Lounkine
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D019295:Computational Biology / Q000379:methods; D016208:Databases, Factual; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D013598:Systems Theory