Recent advances in inducible cyclooxygenase (COX-2) inhibition.
Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances that are involved in several physiological processes but also in pathological conditions such as inflammation. Since ten years now, it is well known that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Observations that COX-1, involved in several homeostatic processes, played a housekeeping role while COX-2 expression was associated with inflammation and other pathologies such as cancer proliferation have led to the development of COX-2 selective inhibitors in order to reduce the classical side-effects, of which gastric irritation is the most common, associated with the use of conventional NSAIDs.
de Leval
X
X
Department of Medicinal Chemistry, University of Liège, 1 av. de l'Hopital, tour 4 (+5) Sart-Tilman, Liège, 4000, Belgium. xdeleval@student.ulg.ac.be
Delarge
J
J
Somers
F
F
de Tullio
P
P
Henrotin
Y
Y
Pirotte
B
B
Dogné
J M
JM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D002986:Clinical Trials as Topic; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000737:chemistry / Q000502:physiology; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases