title: In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.
abstract: A collection of 2150 druggable active sites from the Protein Data Bank was screened by high-throughput docking to identify putative targets for five representative molecules of a combinatorial library sharing a 1,3,5-triazepan-2,6-dione scaffold. Five targets were prioritized for experimental evaluation by computing enrichment in individual protein entries among the top 2% scoring targets. Out of the five proposed proteins, secreted phospholipase A2 (sPLA2) was shown to be a true target for a panel of 1,3,5-triazepan-2,6-diones which exhibited micromolar affinities toward two human sPLA2 members.
authors.affiliation: Bioinformatics of the Drug, CNRS UMR 7175, F-67400 Illkirch, and Immunologie et Chimie Thérapeutiques, CNRS UPR 9021, Institut de Biologie Moléculaire et Cellulaire (IBMC), F-67084 Strasbourg Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Muller
authors.forename: Gersande
authors.initials: G
authors.lastname: Lena
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
authors.forename: Sofiane
authors.initials: S
authors.lastname: Bezzine
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
authors.forename: Didier
authors.initials: D
authors.lastname: Rognan
mesh_terms: D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D030562:Databases, Protein; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054467:Phospholipases A2; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2