Matrix metalloproteinases as valid clinical targets.
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.
Fingleton
Barbara
B
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA. barbara.fingleton@vanderbilt.edu
D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000201:enzymology; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005128:Eye Diseases / Q000188:drug therapy / Q000201:enzymology; D006342:Heart Rupture, Post-Infarction / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000201:enzymology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000201:enzymology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000201:enzymology; D012871:Skin Diseases / Q000188:drug therapy / Q000201:enzymology; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology; D014652:Vascular Diseases / Q000188:drug therapy / Q000201:enzymology
D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases