Is there new hope for therapeutic matrix metalloproteinase inhibition?

Nat Rev Drug Discov. 2014 Dec;13(12):904-27. doi: 10.1038/nrd4390. Epub 2014 Nov 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / drug therapy
  • Inflammation / enzymology
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Matrix Metalloproteinase Inhibitors / chemistry*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Matrix Metalloproteinase Inhibitors / therapeutic use*
  • Matrix Metalloproteinases / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Inflammation Mediators
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases