title: New non-hydroxamic ADAMTS-5 inhibitors based on the 1,2,4-triazole-3-thiol scaffold.
abstract: In this Letter we describe the design, synthesis, screening, and optimization of a new family of ADAMTS-5 inhibitors. These inhibitors display an original 1,2,4-triazole-3-thiol scaffold as a putative zinc binding-group. In vitro results are rationalized by in silico docking of the compounds in ADAMTS-5's crystal structure.
authors.affiliation: INSERM U761 Biostructures and Drug Discovery, Univ. Lille Nord de France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Maingot
authors.forename: Florence
authors.initials: F
authors.lastname: Leroux
authors.forename: Valérie
authors.initials: V
authors.lastname: Landry
authors.forename: Julie
authors.initials: J
authors.lastname: Dumont
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.forename: Bruno
authors.initials: B
authors.lastname: Villoutreix
authors.forename: Olivier
authors.initials: O
authors.lastname: Sperandio
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000071116:ADAMTS5 Protein; D001665:Binding Sites; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D010003:Osteoarthritis / Q000188:drug therapy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D007202:Indicators and Reagents; D011480:Protease Inhibitors; D014230:Triazoles; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human