Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS).

It is an enzyme that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. 

They reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate.

The inhibition of COX can provide relief from the symptoms of inflammation and pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, exert their effects through inhibition of COX. 

Those that are specific to the COX-2 isozyme are called COX-2 inhibitors. 

The active metabolite of paracetamol believed to provide most or all of its analgesic effects is a COX inhibitor, and this is believed to provide part of its effect.

The two isozymes found in humans, PTGS1 and PTGS2, are frequently called COX-1 and COX-2.

COX-1 and COX-2 are of similar molecular weight, approximately 70 and 72 kDa, respectively, and having 65% amino acid sequence homology and near-identical catalytic sites. 

Both proteins have three domains.


Both form dimers.

The membrane anchor fixes the proteins into the endoplasmic reticulum (ER) and microsome membrane.

COX is a common target for anti-inflammatory drugs. 

The most significant difference between the isoenzymes, allowing  for selective inhibition, is the substitution of isoleucine at position 523 in COX-1 with valine in COX-2. 

The main COX inhibitors are the non-steroidal anti-inflammatory drugs.

The classical COX inhibitors are not selective and inhibit all types of COX. 

The resulting inhibition of prostaglandin and thromboxane synthesis has the effect of reduced inflammation, as well as antipyretic, antithrombotic and analgesic effects. 

The most frequent adverse effect of NSAIDs is irritation of the gastric mucosa as prostaglandins have a protective role in the gastrointestinal tract. 

Selectivity for COX-2 is the main feature of celecoxib, etoricoxib, and other members of this drug class. 

COX-2 is usually specific to inflamed tissue, there is much less gastric irritation associated with COX-2 inhibitors, with a decreased risk of peptic ulceration. 

The selectivity of COX-2 does not negate other side-effects of NSAIDs, most notably an increased risk of kidney failure, and there is evidence that indicates an increase in the risk of heart attack, thrombosis, and stroke through an increase of thromboxane unbalanced by prostacyclin.

Rofecoxib was withdrawn in 2004 because of such concerns. 

Prostacyclin is reduced by COX-2 inhibition.

Other COX-2 selective NSAIDs, such as celecoxib, and etoricoxib, are available.

Calcitriol (vitamin D) significantly inhibits the expression of the COX-2 gene.

Caution should be exercised in combining low dose aspirin with COX-2 inhibitors due to potential increased damage to the gastric mucosa. 

COX-2 is upregulated when COX-1 is suppressed with aspirin, which is thought to be important in enhancing mucosal defense mechanisms and lessening the erosion by aspirin.

COX-2 inhibitors have been found to increase the risk of atherothrombosis even with short-term use. 

An analysis of 138 randomized trials and almost 150,000 participants showed that selective COX-2 inhibitors are associated with a moderately increased risk of vascular events: twofold increased risk of myocardial infarction, and also that high-dose regimens of some traditional NSAIDs, such as diclofenac and ibuprofen, but not naproxen are associated with a similar increase in risk of vascular events.

Inhibition of COX-2 reduces the immunosuppressive TGFβ expression in hepatocytes in human hepatocellular carcinoma.

Leave a Reply

Your email address will not be published. Required fields are marked *