Chemically modified tetracyclines as inhibitors of matrix metalloproteinases

Milin R. Acharya, Jürgen Venitz, William D. Figg*, Alex Sparreboom

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Matrix metalloproteinases belong to a diverse group of enzymes that are not only involved in restructuring the extracellular matrix, but also play a major role in various pathophysiological conditions by virtue of their complicated expression, activation, and regulation processes. They have been widely implicated to function as major contenders in cancer progression, frequently due to their role in invasion, proliferation and metastasis. MMP inhibitors have been specifically designed to target these altered activities of MMPs, mostly by means of inhibiting their function and by diminishing their increased expression in various disease states, particularly cancer. Tetracyclines and chemically modified tetracyclines (CMTs) have been rationally designed to inhibit the activity of MMPs and thus decrease the potential risk of spread of tumor cells to distant sites by invasion and metastasis. Pre-clinical and early clinical data for one of these CMTs, COL-3 (formerly CMT-3) indicate considerable potential for this group of anticancer agents. Further testing and rational modifications of these CMT analogues might lead to new anticancer agents.

Original languageEnglish
Pages (from-to)195-208
Number of pages14
JournalDrug Resistance Updates
Volume7
Issue number3
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

  • Anticancer drugs
  • Chemically modified tetracyclines
  • Drug development
  • Matrix metalloproteinase

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