Matrix metalloproteinase inhibitors.
Matrix metalloproteinases (MMPs) are a family of structurally related enzymes that are capable of degrading a wide variety of extracellular matrix proteins. In addition to the role played by these enzymes in normal tissue remodeling, MMPs have been implicted in the pathogenesis of diseases such as rheumatoid arthritis and multiple sclerosis. In cancer increased MMP activity may facilitate tumor invasion, metastasis and tumor angiogenesis. Expression of high levels of MMPs in certain malignancies has been shown to be associated with a poor prognosis. Using structure-based design, a range of low molecular weight synthetic MMP inhibitors have been developed. These have proven effective in animal models of disease and several (CGS 27023A, AG3340, Ro 32-3555 and marimastat) have now commenced clinical trials.