title: Exploring target-selectivity patterns of molecular scaffolds.
abstract: We investigate the question of whether target-selective molecular scaffolds can be identified on the basis of currently available compound activity data. Starting from a pool of 17745 public domain compounds with activity annotations for 433 human targets, we ultimately identify, through a selectivity classification and database-mining approach, 42 molecular scaffolds represented by multiple compounds that are highly selective for a particular target over one or more others. In many other cases, individual compounds representing unique scaffolds are target-selective. Hence, currently available public domain compound selectivity data are sparse. However, we also identify selectivity patterns that evolve around specific targets and are formed by multiple target-selective scaffolds. These scaffolds should provide interesting starting points for further chemical exploration.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
keywords: Molecular selectivity; compound database mining; privileged substructures; selectivity patterns; target family selective molecular scaffolds; target-selective scaffolds