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

Aspirin-like molecules that covalently inactivate cyclooxygenase-2.

Many of aspirin's therapeutic effects arise from its acetylation of cyclooxygenase-2 ( COX-2), whereas its antithrombotic and ulcerogenic effects result from its acetylation of COX-1. Here, aspirin-like molecules were designed that preferentially acetylate and irreversibly inactivate COX-2. The most potent of these compounds was o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS). Relative to aspirin, APHS was 60 times as reactive against COX-2 and 100 times as selective for its inhibition; it also inhibited COX-2 in cultured macrophages and colon cancer cells and in the rat air pouch in vivo. Such compounds may lead to the development of aspirin-like drugs for the treatment or prevention of immunological and proliferative diseases without gastrointestinal or hematologic side effects.[1]

References

  1. Aspirin-like molecules that covalently inactivate cyclooxygenase-2. Kalgutkar, A.S., Crews, B.C., Rowlinson, S.W., Garner, C., Seibert, K., Marnett, L.J. Science (1998) [Pubmed]
 
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