Mechanisms to inhibit matrix metalloproteinase activity: Where are we in the development of clinically relevant inhibitors?

Christian A. Corbitt, Jing Lin, Merry L. Lindsey

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention. Although numerous drug therapies to inhibit MMPs have been explored, only one agent (doxycycline hyclate) is currently approved for clinical use. Multiple reasons potentially explain the lack of success in developing MMP inhibitors, including issues with selectivity and specificity and the presence of multiple substrates with conflicting functions. Major recent advances in the MMP field include an increased understanding of MMP biology, the improved establishment of parameters to adequately evaluate efficacy, and methods to enhance inhibitor design. This review will explore the latest research and patents targeted at MMP inhibition, and will focus on both direct and indirect mechanisms to block MMPs.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalRecent Patents on Anti-Cancer Drug Discovery
Volume2
Issue number2
DOIs
StatePublished - Jun 2007

Keywords

  • Cancer
  • Hydroxamate
  • MMP inhibitors
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Cancer Research
  • Pharmacology (medical)

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