Authors: Tortorella, Micky D.; Malfait, Fransiska; Barve, Ruteja A.; Shieh, Huey-Sheng; Malfait, Anne-Marie

Source: Current Pharmaceutical Design, Volume 15, Number 20, July 2009 , pp. 2359-2374(16)

Publisher: Bentham Science Publishers

Abstract:

The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family of metalloproteases consists of 19 members. These enzymes play an important role in the turnover of extracellular matrix proteins in various tissues and their altered regulation has been implicated in diseases such as cancer, arthritis and atherosclerosis. Unlike other metalloproteinases, ADAMTS members demonstrate a narrow substrate specificity due to the various exosites located in the C-terminal regions of the enzymes, which influence protein recognition and matrix localization. The tight substrate specificity exhibited by ADAMTS enzymes makes them potentially safe pharmaceutical targets, as selective inhibitors designed for each member will result in the inhibition or cleavage of only a limited number of proteins. With the recent elucidation of crystal structures for ADAMTS-1, -4 and -5, the design of potent and selective small molecule inhibitors is underway and will lead to drug candidates for evaluation in clinical trials in the next 5-10 years.

Keywords: ADAMTS; metalloproteinase; aggrecanase

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209788682433

Affiliations: 1: Pfizer Global Research and Development 700 Chesterfield Parkway, Chesterfield, MO 63017, USA.

Publication date: 2009-07-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Tortorella, Micky D. ;  Malfait, Fransiska ;  Barve, Ruteja A. ;  Shieh, Huey-Sheng ;  Malfait, Anne-Marie

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers