Aspirin-like molecules that covalently inactivate cyclooxygenase-2

Amit S. Kalgutkar, Brenda C. Crews, Scott W. Rowlinson, Carlos Garner, Karen Seibert, Lawrence J. Marnett

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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-(acetoxy-phenyl)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.

Original languageEnglish
Pages (from-to)1268-1270
Number of pages3
Issue number5367
StatePublished - May 22 1998

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    Kalgutkar, A. S., Crews, B. C., Rowlinson, S. W., Garner, C., Seibert, K., & Marnett, L. J. (1998). Aspirin-like molecules that covalently inactivate cyclooxygenase-2. Science, 280(5367), 1268-1270.