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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Humes, J.L. et al.

Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents.

Evidence is presented to show that nonsteroidal antiinflammatory drugs react with two sites on the cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1). Although the degree of interaction with the catalytic site determines the potency of such compounds, interaction with the supplementary site is also obligatory for efficacy as cyclooxygenase inhibitors and may explain the selectivity of such drugs in inhibiting the cyclooxygenase but not the lipoxygenase pathway. Drugs that interact more effectively with the supplementary site than with the catalytic site--i.e., those of weak to moderate activity as cyclooxygenase inhibitors--are shown to prevent inhibition of the enzyme by indomethacin. Compounds in this class are also capable of blocking the ulcerogenic action of indomethacin, which suggests that this antiulcerogenic property stems from a direct action at the level of the cyclooxygenase in the stomach.[1]

References

Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents. Humes, J.L., Winter, C.A., Sadowski, S.J., Kuehl, F.A. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]

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