title: Method for the evaluation of structure-activity relationship information associated with coordinated activity cliffs.
abstract: Activity cliffs are generally defined as pairs of active compounds having a large difference in potency. Although this definition of activity cliffs focuses on compound pairs, the vast majority of cliffs are formed in a coordinated manner. This means that multiple highly and weakly potent compounds form series of activity cliffs, which often overlap. In activity cliff networks, coordinated cliffs emerge as disjoint activity cliff clusters. Recently, we have identified all cliff clusters from current bioactive compounds and analyzed their topologies. For structure-activity relationship (SAR) analysis, activity cliff clusters are of high interest, since they contain more SAR information than cliffs that are individually considered. For medicinal chemistry applications, a key question becomes how to best extract SAR information from activity cliff clusters. This represents a challenging problem, given the complexity of many activity cliff configurations. Herein we introduce a generally applicable methodology to organize activity cliff clusters on the basis of structural relationships, prioritize clusters, and systematically extract SAR information from them.
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: Dilyana
authors.initials: D
authors.lastname: Dimova
authors.forename: Dagmar
authors.initials: D
authors.lastname: Stumpfe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D016000:Cluster Analysis; D062126:Databases, Chemical; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations