Cathepsin S inhibitors

Cysteine proteases have attracted considerable interest over the past decade. Lysosomal cysteine protease cathepsin S plays an important role in antigen presentation and matrix degradation. Interest for this enzyme has recently grown and similar to 70 patents have appeared over the last 3 years, targeting cathepsin S either solely or among other related cysteine proteases. With the rapidly growing understanding of the pharmacology of cathepsin S, a number of pharmaceutical companies have reported to be actively seeking inhibitors to treat inflammatory and autoimmune diseases. The major players in this field are Aventis Pharmaceuticals in collaboration with Celera Genomics (previously Axys pharmaceuticals), Boehringer Ingelheim and Glaxo SmithKline. These companies report compounds undergoing preclinical evaluation. Most of the disclosed inhibitors contain an electrophilic warhead, such as nitriles, activated ketones, aldehydes and beta-lactams, that interacts with the catalytic cysteine thiol.