The design, structure, and therapeutic application of matrix metalloproteinase inhibitors

Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes in volved in the degradation and remodeling of extracellular matrix proteins. The activities of these enzymes are well regulated by endogenous tissue inh ibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activitie s due to an imbalance in the levels of MMPs and TIMPs has been implicated i n the pathogenesis of a variety of diseases such as cancer. osteoarthritis, acid rheumatoid arthritis. Thus, MMP inhibitors are expected to be useful for the treatment of these disorders. This article reviews briefly the bioc hemistry of MMPs and evidence for their pathogenic roles using molecular bi ology approaches. Biomolecular structures used in the design of MMP inhibit ors are thoroughly covered. Major emphasis is on recently published potent, small molecular weight MMP inhibitors and their pharmacological properties . Finally, available clinical results of compounds in development are summa rized.