Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity.

Original publication

DOI

10.1016/j.ejmech.2012.12.058

Type

Journal article

Journal

Eur J Med Chem

Publication Date

04/2013

Volume

62

Pages

379 - 394

Keywords

ADAM Proteins, ADAMTS4 Protein, ADAMTS5 Protein, Dose-Response Relationship, Drug, Humans, Matrix Metalloproteinase Inhibitors, Matrix Metalloproteinases, Models, Molecular, Molecular Structure, Osteoarthritis, Procollagen N-Endopeptidase, Protease Inhibitors, Structure-Activity Relationship, Sulfonamides