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Year : 1999  |  Volume : 31  |  Issue : 5  |  Page : 322-332

Cyclooxygenase-2: A new therapeutic target

Correspondence Address:
S Sengupta

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Source of Support: None, Conflict of Interest: None

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Cyclooxygenase (COX) is the enzyme catalysing oxidation of arachidonic acid to hydroperoxy endoperoxide (PGG2) and its subsequent reduction to hydroxy endoperoxide (PGH2). It is thus an important therapeutic target for the modulation of the prostaglandin pathway. Recent studies have demonstrated the existence of a second isoform of COX. Both the isoforms have a molecular weight of 71K with 63% amino acid homology. The human COX-2 gene is however a 8.3Kb small immediate early gene and is induced by most of the stimuli associated with inflammation. COX-2 has thus been implicated in pathological roles of COX while constitutive COX-1 is said to be involved in physiological functions. Indeed, COX-2 has now been associated with inflammation, hyperalgesia, angiogenesis, neuromodulation, cancer and Alzheimer's disease, giving rise to the opportunity of modulating these conditions with selective inhibitors of COX-2. The recent X-ray structural analysis for COX-2 has paved the way for development of a whole new range of agents with selectivity for this isoform, thereby sparing the physiological functions. Here in this review, an attempt has been made to elucidate the role of COX-2 in these conditions and to evaluate the various COX-2 inhibitors that are in different stages of development or are presently available. From the present knowledge of COX-1 and COX-2 an effort has been made to reclassify NSAIDs based on the selectivity in inhibiting the isoforms.


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