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Progress in the Development of Matrix Metalloproteinase Inhibitors

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Abstract:

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation and remodeling of extracellular matrix proteins that are associated with the tumorigenic process. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function.Thus, MMP inhibitors (MMPIs) are expected to be useful for the treatment of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. A vast number of MMPIs have been developed in recent years.With the failure of these inhibitors in clinical trials,more efforts have been directed to the design of specific inhibitors with different Zn-binding groups. This review summarizes the current status of MMPIs, the design of small molecular weight MMPIs , a brief description of available threedimensional MMP structures, a review of the proposed therapeutic utility of MMPIs, and a clinical update of compounds that have entered clinical trials in humans.

Keywords: MMP inhibitors; Matrix metalloproteinases; Zinc-binding groups; angiogenesis; cancer; computer-aided drug design; metastasis; proteases

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708784567680

Affiliations: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, ShanDong University, 44, West Culture Road, Ji’nan, 250012, P.R. China.

Publication date: June 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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