COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease

Lancet. 2000 Feb 19;355(9204):646-8. doi: 10.1016/S0140-6736(99)12031-2.


A new generation of non-steroidal anti-inflammatory drugs has been described that selectively targets the inducible isoform of cyclo-oxygenase, cyclo-oxygenase 2 (COX-2). This isoform is expressed at sites of inflammation, which has led to the speculation that its inhibition could provide all the benefits of current nonsteroidal anti-inflammatory drugs, but without their major side-effects on the gastrointestinal system (which are due to inhibition of COX-1). We have shown that COX-2 (identified by use of specific antibodies) is induced during the resolution of an inflammatory response, inhibition of COX-2 resulting in persistence of the inflammation due to the prevention of the synthesis of a range of anti-inflammatory prostanoids. We propose that there is a third isoform of this enzyme family, COX-3, a proposal that will have implication for the prescription of both existing and new generation anti-inflammatory drugs, and might represent a new therapeutic target.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Isoenzymes / pharmacology*
  • Membrane Proteins
  • Peroxidases / antagonists & inhibitors
  • Prostaglandin-Endoperoxide Synthases / chemistry
  • Prostaglandin-Endoperoxide Synthases / pharmacology*
  • Protein Isoforms


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Protein Isoforms
  • Peroxidases
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases