New non-hydroxamic ADAMTS-5 inhibitors based on the 1,2,4-triazole-3-thiol scaffold.

Journal article

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: Maingot, L; Leroux, F; Landry, V; Dumont, J; Nagase, H

• Publication status: Published
• Journal: Bioorganic and medicinal chemistry letters
• Volume: 20
• Issue: 21
• Pages: 6213-6216
• Publication date: 2010-11-01
• DOI: 10.1016/j.bmcl.2010.08.108
• EISSN: 1464-3405
• ISSN: 0960-894X
• Language: English
• Keywords: Humans; X-Ray Diffraction; Binding Sites; Indicators and Reagents; Protease Inhibitors; Protein Conformation; Protein Binding; Triazoles; Osteoarthritis; ADAM Proteins; Models, Molecular; Drug Evaluation, Preclinical; Computer Simulation; Structure-Activity Relationship