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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Cyclooxygenase-2 Biology

Author(s): Joan Claria

Volume 9 , Issue 27 , 2003

Page: [2177 - 2190] Pages: 14

DOI: 10.2174/1381612033454054

Price: $65


In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid from membrane phospholipids in response to the interaction of a stimulus with a receptor on the cell surface. Arachidonic acid is subsequently transformed by the enzyme cyclooxygenase (COX) to prostaglandins (PGs) and thromboxane (TX). The COX pathway is of particular clinical relevance because it is the major target for non-steroidal anti-inflammatory drugs, which are commonly used for relieving inflammation, pain and fever. In 1991, it was disclosed that COX exists in two distinct isozymes (COX-1 and COX-2), one of which, COX-2, is primarily responsible for inflammation but apparently not for gastrointestinal integrity or platelet aggregation. For this reason, in recent years, novel compounds that are selective for this isozyme, the so-called selective COX-2 inhibitors or COXIBs, which retain anti-inflammatory activity but minimize the risk of gastrointestinal toxicity and bleeding, have been developed. This review article provides an overview and an update on the progress achieved in the area of COX-2 and PG biosynthesis and describes the role of COX-2 in health and disease. It also discusses some unresolved issues related to the use of selective COX-2 inhibitors as a safe and promising therapeutic option not only for the treatment of inflammatory states but also for cancer.

Keywords: eicosanoids, prostaglandins, cyclooxygenase-2, non-steroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, gastrointestinal tract

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