title: Structure-Promiscuity Relationship Puzzles-Extensively Assayed Analogs with Large Differences in Target Annotations.
abstract: Publicly available screening data were systematically searched for extensively assayed structural analogs with large differences in the number of targets they were active against. Screening compounds with potential chemical liabilities that may give rise to assay artifacts were identified and excluded from the analysis. "Promiscuity cliffs" were frequently identified, defined here as pairs of structural analogs with a difference of at least 20 target annotations across all assays they were tested in. New assay indices were introduced to prioritize cliffs formed by screening compounds that were extensively tested in comparably large numbers of assays including many shared assays. In these cases, large differences in promiscuity degrees were not attributable to differences in assay frequency and/or lack of assay overlap. Such analog pairs have high priority for further exploring molecular origins of multi-target activities. Therefore, these promiscuity cliffs and associated target annotations are made freely available. The corresponding analogs often represent equally puzzling and interesting examples of structure-promiscuity relationships.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 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 Bonn, Dahlmannstr. 2, 53113, Bonn, Germany.
authors.forename: Swarit
authors.initials: S
authors.lastname: Jasial
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113, Bonn, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Gilberg
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113, Bonn, Germany. bajorath@bit.uni-bonn.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations
keywords: assay profiles; biological screening; multi-target activities; promiscuity cliffs; structure-promiscuity relationships