title: Graph mining for SAR transfer series.
abstract: The transfer of SAR information from one analog series to another is a difficult, yet highly attractive task in medicinal chemistry. At present, the evaluation of SAR transfer potential from a data mining perspective is still in its infancy. Only recently, a first computational approach has been introduced to evaluate SAR transfer events. Here, a substructure relationship-based molecular network representation has been used as a starting point to systematically identify SAR transfer series in large compound data sets. For this purpose, a methodology is introduced that consists of two stages. For graph mining, an algorithm has been designed that extracts all parallel series from compound data sets. A parallel series is formed by two series of analogs with different core structures but pairwise corresponding substitution patterns. The SAR transfer potential of identified parallel series is then evaluated using a scoring function that emphasizes corresponding potency progression over many analog pairs and large potency ranges. The substructure relationship-based molecular network in combination with the graph mining algorithm currently represents the only generally applicable approach to systematically detect SAR transfer events in large compound data sets. The combined approach has been evaluated on a large number of compound data sets and shown to systematically identify SAR transfer series.
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: Disha
authors.initials: D
authors.lastname: Gupta-Ostermann
authors.forename: Mathias
authors.initials: M
authors.lastname: Wawer
authors.forename: Anne Mai
authors.initials: AM
authors.lastname: Wassermann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D000465:Algorithms; D000991:Antithrombins / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D057225:Data Mining; D062126:Databases, Chemical; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D011485:Protein Binding; D012107:Research Design; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D000991:Antithrombins; D054852:Small Molecule Libraries; D013917:Thrombin