BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in cas...

Colorectal cancer (CRC) is a leading cause of cancer death, yet primary prevention remains the best approach to reducing overall morbidity and mortality. There is a clear molecular link between cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production and CRC progression. Although selective COX-2 inhibitors as well as non-steroidal anti-inflammatory drugs (NSAIDs) reduce the number an...

Cancer is the second most common cause of death in the world, and primary prevention remains the best approach to reducing overall morbidity and mortality. There is a molecular link between cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production and colonic tumorigenesis. Selective COX-2 inhibitors as well as non-steroidal anti-inflammatory drugs (NSAIDs) reduce the number and sizes...

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expres...

The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational tec...

Cyclo-oxygenase-2 selective inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of acute cardiovascular events. Only aspirin offers primary and secondary cardiovascular prophylaxis, but trials have not answered directly whether low-dose aspirin is cardioprotective with COX-2 inhibitors. A large inception cohort study showed that concomi...

For many years, cyclooxygenase-2 (COX-2), a critical enzyme for PG production, has been the favorite target for anti-inflammatory drug development. However, recent revelations regarding the adverse effects of selective COX-2 inhibitors have stimulated intense debate. Interestingly, in the early phase of inflammation, COX-2 facilitates inflammatory PG production while in the late phase it has an...

Cyclooxygenase (COX) -1 and COX-2 are expressed in airway cells, where their activities influence functions such as airway hyperreactivity. Clinical data show that mixed COX-1/COX-2 inhibitors such as aspirin, but not COX-2 selective inhibitors such as rofecoxib, induce bronchoconstriction and asthma in sensitive individuals. This anomaly has not yet been explained. Here, we have used tissue fr...

A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC(50) = 0.077 μ...

Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pa...