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