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| Aspirin-like molecules that covalently inactivate cyclooxygenase-2 |
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| Author(s): Kalgutkar AS, Crews BC, Rowlinson SW, Garner C, Seibert K, Marnett LJ |
| Source: SCIENCE Volume: 280 Issue: 5367 Pages: 1268-1270 Published: MAY 22 1998 |
| Times Cited: 160 References: 24 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Marnett, LJ (reprint author), Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Canc Ctr, Ctr Mol Toxicol,Dept Biochem, Nashville, TN 37232 USA |
Addresses:
1. Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Canc Ctr, Ctr Mol Toxicol,Dept Biochem, Nashville, TN 37232 USA
2. Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Canc Ctr, Ctr Mol Toxicol,Dept Chem, Nashville, TN 37232 USA
3. Searle Monsanto, St Louis, MO 63167 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: ZQ351 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |