Recent advances in the search for novel 5-lipoxygenase inhibitors for the treatment of asthma

Eur J Med Chem. 2018 Jun 10:153:65-72. doi: 10.1016/j.ejmech.2017.10.020. Epub 2017 Oct 10.

Abstract

The products of 5-lipoxygenase are synthesized and released in the airway when an asthmatic reaction occurs. 5-lipoxygenase via arachidonic acid metabolism produces leukotrienes that mediate bronchoconstriction and inflammatory modifications essential in the pathophysiology of asthma. Until to now, only one approved 5-LO inhibitor, zileuton, can be found as a potential therapy for asthma. With the increasing number of indications for anti-leukotriene (anti-LT) drugs, the development of 5-LO inhibitor agents becomes increasingly important. The present MiniReview reports an update on 5-LO inhibitors currently under clinical investigation. In addition, the latest advances focused on the development of new 5-lipoxygenase inhibitors as asthma anti-inflammatory agents are also discussed.

Keywords: 5-lipoxygenase; Airway hyperresponsiveness; Asthma; Inflammation; Leukotrienes.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Arachidonate 5-Lipoxygenase / immunology
  • Arachidonate 5-Lipoxygenase / metabolism
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / metabolism
  • Clinical Trials as Topic
  • Drug Discovery
  • Humans
  • Leukotrienes / immunology
  • Leukotrienes / metabolism
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / pharmacology
  • Lipoxygenase Inhibitors / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Leukotrienes
  • Lipoxygenase Inhibitors
  • Arachidonate 5-Lipoxygenase