Abstract
Abstract: Remodeling of the extracellular matrix (ECM) has been implicated in a variety of human diseases. Upregulation of matrix metalloproteinases (MMPs), a family of at least 14 zinc-dependent enzymes which catabolize the ECM, appear to play a critical role in this process. Initial work, focussed on the synthesis of peptide hydroxamates, which were broad spectrum MMP inhibitors for the treatment of arthritis and cancer. The current generation of MMP inhibitors address bioavailability and selectivity, and the therapeutic potential has expanded. This review covers the evidence for the pathological role of MMP's and TIMP's across several therapeutic areas including atherosclerosis, neurodegenerative disease, heart failure and wound healing, and the development of selective MMP inhibitors.
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