COX-3 the enzyme and the concept: steps towards highly specialized pathways and precision therapeutics?

Prostaglandins Leukot Essent Fatty Acids. 2003 Nov;69(5):339-43. doi: 10.1016/j.plefa.2003.07.003.


Cyclooxygenases (COXs) catalyse the key rate-limiting step in prostanoid and thromboxane biosynthesis and are targets of non-steroidal anti-inflammatory drugs (NSAIDs). Until recently, the presence of only two isoforms-COX-1 and COX-2-remained in question because the potent anti-pyretic and analgesic effects of acetaminophen (paracetamol, tylenol ben-u-ron) could not be explained by either COX-1 or COX-2 blockades. A novel COX-1 splice variant termed COX-3, sensitive to acetaminophen, was recently discovered by Simmons et al., and is considered to play a key role in the biosynthesis of prostanoids known to be important mediators in pain and fever. Drugs that preferential block COX-1 also appear to act at COX-3. However the existence of COX-3 at the nucleotide sequence level in humans has been called to question. A functional COX-3 in humans is still to come underlining that the concept of COX-3 is still attractive. Here, we discuss some of the implications drawn from the identification of additional functional cyclooxygenase members in the generation of bioactive autacoids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetaminophen / metabolism
  • Analgesics, Non-Narcotic / metabolism
  • Animals
  • Cyclooxygenase 1
  • Cyclooxygenase Inhibitors / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / immunology
  • Prostaglandin-Endoperoxide Synthases / metabolism*


  • Analgesics, Non-Narcotic
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Acetaminophen
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • cyclooxygenase-3