TY - JOUR
T1 - A review of the ADAMTS family, pharmaceutical targets of the future
AU - Tortorella, Micky D.
AU - Malfait, Fransiska
AU - Barve, Ruteja A.
AU - Shieh, Huey Sheng
AU - Malfait, Anne Marie
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - ADAMTS
KW - Aggrecanase
KW - Metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=69249153030&partnerID=8YFLogxK
U2 - 10.2174/138161209788682433
DO - 10.2174/138161209788682433
M3 - Review article
C2 - 19601837
AN - SCOPUS:69249153030
SN - 1381-6128
VL - 15
SP - 2359
EP - 2374
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 20
ER -