Abstract
Prostaglandin endoperoxide synthase (PGHS) catalyzes the first two steps of the arachidonic acid cascade leading to prostaglandin and thromboxane biosynthesis.1 Two distinct PGHS isozymes exist in mammals.2 PGHS-1 is constitutively expressed and involved in the synthesis of cytoprotective prostaglandins in the stomach and thromboxanes in platelets, whereas PGHS-2 is inducible and is a major contributor to prostaglandin biosynthesis in inflammatory cells and in the brain.3 The differential tissue distribution of the isozymes provides a basis for the development of selective PGHS-2 or COX-2 inhibitors as antiinflammatory and analgesic agents without the gastrointestinal and vascular liabilities that plague all currently available NSAIDs. Most COX-2 inhibitors developed to date, including the diarylheterocycles4 and the acidic sulfonamides5, inhibit the enzyme by binding tightly but noncovalently at the cyclooxygenase active site.6
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Kalgutkar, A.S., Crews, B.C., Rowlinson, S.W., Garner, C., Marnett, L.J. (1999). Discovery of a New Class of Selective Cyclooxygenase-2 (COX-2) Inhibitor that Covalently Modifies the Isozyme. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_21
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DOI: https://doi.org/10.1007/978-1-4615-4793-8_21
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