Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, EC 1.14.99.1) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid.
[3] Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, exert their effects through inhibition of COX.
Drug molecules, such as DuP-697 and the coxibs derived from it, bind to this alternative site and are considered to be selective inhibitors of COX-2.
The most frequent adverse effect of NSAIDs is irritation of the gastric mucosa as prostaglandins normally have a protective role in the gastrointestinal tract.
Because 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.
[14] Caution should be exercised in combining low dose aspirin with COX-2 inhibitors due to potential increased damage to the gastric mucosa.
This evidence, however, has been contradicted by the 2016 PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen) trial[17] of 24,081 participants, which shows a lower incidence of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke for Celecoxib as compared to both Naproxen and Ibuprofen.
[12] Inhibition of COX-2 using celecoxib has been shown to reduce the immunosuppressive TGFβ expression in hepatocytes attenuating EMT in human hepatocellular carcinoma[18]