A review of the ADAMTS family, pharmaceutical targets of the future

Micky D. Tortorella, Fransiska Malfait, Ruteja A. Barve, Huey Sheng Shieh, Anne Marie Malfait

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations

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.

Original languageEnglish
Pages (from-to)2359-2374
Number of pages16
JournalCurrent Pharmaceutical Design
Volume15
Issue number20
DOIs
StatePublished - 2009

Keywords

  • ADAMTS
  • Aggrecanase
  • Metalloproteinase

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