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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Progress in the Development of Matrix Metalloproteinase Inhibitors

Author(s): GuoGang Tu, WenFang Xu, HuiMing Huang and ShaoHua Li

Volume 15, Issue 14, 2008

Page: [1388 - 1395] Pages: 8

DOI: 10.2174/092986708784567680

Price: $65


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

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