Matrix metalloproteinases as valid clinical targets

Curr Pharm Des. 2007;13(3):333-46. doi: 10.2174/138161207779313551.

Abstract

The matrix metalloproteinase family of enzymes has been a pharmaceutical target for over 20 years. In that time, many drugs have been developed but none have successfully passed clinical trials. A significant problem has been development of dose-limiting side-effects that were revealed during long-term clinical trials in diseases such as arthritis and various cancers. There are, however, other clinical settings where evidence for MMP function contributing to the pathophysiology of disease is strong. A number of these settings will be discussed here together with evidence from animal models that MMP inhibition is a valid strategy to be considered. A major advantage with many of these settings is that drug exposure may not have to be long-term and/or systemic thus reducing the possibility that side-effects will stymie MMPI-based therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis / drug therapy
  • Arthritis / enzymology
  • Atherosclerosis / drug therapy
  • Atherosclerosis / enzymology
  • Drug Design*
  • Extracellular Matrix Proteins / metabolism
  • Eye Diseases / drug therapy
  • Eye Diseases / enzymology
  • Heart Rupture, Post-Infarction / drug therapy
  • Heart Rupture, Post-Infarction / enzymology
  • Humans
  • Hypertrophy, Left Ventricular / drug therapy
  • Hypertrophy, Left Ventricular / enzymology
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / metabolism
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / enzymology
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protease Inhibitors / pharmacology*
  • Protease Inhibitors / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Respiratory Distress Syndrome, Adult / drug therapy
  • Respiratory Distress Syndrome, Adult / enzymology
  • Skin Diseases / drug therapy
  • Skin Diseases / enzymology
  • Stroke / drug therapy
  • Stroke / enzymology
  • Vascular Diseases / drug therapy
  • Vascular Diseases / enzymology

Substances

  • Extracellular Matrix Proteins
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Matrix Metalloproteinases