Advances in cathepsin S inhibitor design.
Cathepsin S is expressed in antigen-presenting cells and plays a role in invariant chain processing and major histocompatibility complex class II (MHCII) antigen presentation leading to CD4+ T-cell activation. An oral cathepsin S inhibitor that blocks MHCII antigen presentation could result in a T-cell-selective immunosuppressant agent with improved safety over the current standard of care for the treatment of rheumatoid arthritis, psoriasis, multiple sclerosis and other autoimmune-based inflammatory diseases. This review focuses on advances in cathepsin S inhibitor utility and design since January of 2004.
Link
John O
JO
Gilead Sciences Inc, 344 Lakeside Drive, Foster City, CA 94404, USA. john.link@gilead.com
Zipfel
Sheila
S
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000201:enzymology; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*
D004791:Enzyme Inhibitors; D002403:Cathepsins; C028217:cathepsin S