Is there new hope for therapeutic matrix metalloproteinase inhibition?
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a family of 24 members in mammals. Evidence of the pathological roles of MMPs in various diseases, combined with their druggability, has made them attractive therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs in cancer progression, and more than 50 MMP inhibitors have been investigated in clinical trials in various cancers. However, all of these trials failed. Reasons for failure include the lack of inhibitor specificity and insufficient knowledge about the complexity of the disease biology. MMPs are also known to be involved in several inflammatory processes, and there are new therapeutic opportunities for MMP inhibitors to treat such diseases. In this Review, we discuss the recent advances made in understanding the role of MMPs in inflammatory diseases and the therapeutic potential of MMP inhibition in those conditions.
1] Inflammation Research Center - VIB, Rijvisschestraat 120 9052 Ghent, Belgium. [2] Department of Biomedical Molecular Biology - Ghent University, FSVM Building, Technologiepark 927, B-9052 Zwijnaarde, Ghent, Belgium.
Roosmarijn E
RE
Vandenbroucke
1] Inflammation Research Center - VIB, Rijvisschestraat 120 9052 Ghent, Belgium. [2] Department of Biomedical Molecular Biology - Ghent University, FSVM Building, Technologiepark 927, B-9052 Zwijnaarde, Ghent, Belgium.
Claude
C
Libert
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases