Designing therapeutically effective 5-lipoxygenase inhibitors

Trends Pharmacol Sci. 1992 Aug;13(8):323-30. doi: 10.1016/0165-6147(92)90100-k.

Abstract

Metabolism of arachidonic acid by the enzyme 5-lipoxygenase leads to the formation of a group of biologically active lipids known as leukotrienes. Peptidoleukotrienes are powerful bronchoconstrictor agents while leukotriene B4 is a potent chemotactic agent for a variety of leukocytes. In view of these properties, leukotrienes have been proposed as important mediators in allergic and inflammatory disorders, and inhibitors of 5-lipoxygenase, by blocking leukotriene synthesis, have therapeutic potential in a range of diseases including arthritis and asthma. This review by Rodger McMillan and Ed Walker summarizes the biology of leukotrienes and the current knowledge of the mechanism of 5-lipoxygenase, providing a framework for consideration of the discovery, development and clinical status of drugs in the three major classes of 5-lipoxygenase inhibitors: 'redox' inhibitors, iron ligand inhibitors and 'non-redox' inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Arachidonic Acid / metabolism*
  • Drug Design
  • Ferric Compounds / metabolism
  • Humans
  • Leukotrienes / metabolism*
  • Lipoxygenase Inhibitors* / pharmacokinetics
  • Lipoxygenase Inhibitors* / pharmacology*
  • Lipoxygenase Inhibitors* / therapeutic use
  • Oxidation-Reduction

Substances

  • Ferric Compounds
  • Leukotrienes
  • Lipoxygenase Inhibitors
  • Arachidonic Acid
  • Arachidonate 5-Lipoxygenase