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...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1998-05, Vol.280 (5367), p.1268-1270 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1270 |
|---|---|
| container_issue | 5367 |
| container_start_page | 1268 |
| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 280 |
| creator | Kalgutkar, Amit S. Crews, Brenda C. Rowlinson, Scott W. Garner, Carlos Seibert, Karen Marnett, Lawrence J. |
| description | 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. |
| doi_str_mv | 10.1126/science.280.5367.1268 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_743468149</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A20813437</galeid><jstor_id>2896076</jstor_id><sourcerecordid>A20813437</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-520d1516ea55dae13865fb7c6f0e1a91724b50574c75cad09f886bba61cfcb933</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhS0EKkPhH1ApQhVsyOBH_MhyiHhUKuoG1pbjuRk8eOwhdqrOv8fRREViwepKPt-9OscHoSuC14RQ8SFZB8HCmiq85kzIdXlUT9CK4JbXLcXsKVphzEStsOTP0YuU9hgXrWUX6KIMwRVZoY-bdHSjC7V3v6D6Fj3YyUOq8k-Tqy7eGw8h-1N1E4zN7t5kqLqT9TE-nHYQTIKavkTPBuMTvFrmJfrx-dP37mt9e_flptvc1pYTmmtO8ZZwIsBwvjVAmBJ86KUVAwZiWiJp03PMZWMlt2aL20Ep0fdGEDvYvmXsEr073z2O8fcEKeuDSxa8NwHilLRsWCMUadpCvv0vSQQr6dV88s0_4D5OYygpNCWseMGMF-j9GdqVz9Au2BgyPGQbvYcd6JKxu9MbihVhDZMF52fcjjGlEQZ9HN3BjCdNsJ6b00tzujSn5-b03FzZu1q8TP0Bto9bS1VFv150k6zxw2iCdekRo0zippndvj5j-5Tj-FdWrcBSsD9OPqpF</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213574035</pqid></control><display><type>article</type><title>Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2</title><source>American Association for the Advancement of Science</source><source>Jstor Complete Legacy</source><source>MEDLINE</source><creator>Kalgutkar, Amit S. ; Crews, Brenda C. ; Rowlinson, Scott W. ; Garner, Carlos ; Seibert, Karen ; Marnett, Lawrence J.</creator><creatorcontrib>Kalgutkar, Amit S. ; Crews, Brenda C. ; Rowlinson, Scott W. ; Garner, Carlos ; Seibert, Karen ; Marnett, Lawrence J.</creatorcontrib><description>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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.280.5367.1268</identifier><identifier>PMID: 9596581</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Acetylation ; Acetylene - analogs & derivatives ; Acetylene - chemical synthesis ; Acetylene - chemistry ; Acetylene - pharmacology ; Alkynes ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Aspirin ; Aspirin - chemistry ; Aspirin - pharmacology ; Binding Sites ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Cell Division - drug effects ; Cell growth ; Cell Line ; Colonic Neoplasms - enzymology ; Colonic Neoplasms - pathology ; Colorectal cancer ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase inhibitors ; Cyclooxygenase Inhibitors - chemical synthesis ; Cyclooxygenase Inhibitors - chemistry ; Cyclooxygenase Inhibitors - pharmacology ; Dinoprostone - biosynthesis ; Drug Design ; Enzyme inhibitors ; Enzymes ; Health aspects ; Humans ; Indomethacin - pharmacology ; Inhibition ; Inhibitory concentration 50 ; Innovations ; Ions ; Isoenzymes - chemistry ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Macrophages ; Macrophages - enzymology ; Medical research ; Medical sciences ; Membrane Proteins ; Mice ; Molecules ; Mutagenesis, Site-Directed ; Nonsteroidal anti-inflammatory agents ; Nonsteroidal anti-inflammatory drugs ; Pharmacology. Drug treatments ; Prostaglandin D2 - biosynthesis ; Prostaglandin-Endoperoxide Synthases - chemistry ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Prostaglandins ; Rats ; Rats, Inbred Lew ; Sulfides ; Sulfides - chemical synthesis ; Sulfides - chemistry ; Sulfides - pharmacology ; Thromboxane B2 - biosynthesis ; Tumor Cells, Cultured</subject><ispartof>Science (American Association for the Advancement of Science), 1998-05, Vol.280 (5367), p.1268-1270</ispartof><rights>Copyright 1998 American Association for the Advancement of Science</rights><rights>1998 INIST-CNRS</rights><rights>COPYRIGHT 1998 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science May 22, 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-520d1516ea55dae13865fb7c6f0e1a91724b50574c75cad09f886bba61cfcb933</citedby><cites>FETCH-LOGICAL-c512t-520d1516ea55dae13865fb7c6f0e1a91724b50574c75cad09f886bba61cfcb933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2896076$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2896076$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2370445$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9596581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kalgutkar, Amit S.</creatorcontrib><creatorcontrib>Crews, Brenda C.</creatorcontrib><creatorcontrib>Rowlinson, Scott W.</creatorcontrib><creatorcontrib>Garner, Carlos</creatorcontrib><creatorcontrib>Seibert, Karen</creatorcontrib><creatorcontrib>Marnett, Lawrence J.</creatorcontrib><title>Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Acetylation</subject><subject>Acetylene - analogs & derivatives</subject><subject>Acetylene - chemical synthesis</subject><subject>Acetylene - chemistry</subject><subject>Acetylene - pharmacology</subject><subject>Alkynes</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Aspirin</subject><subject>Aspirin - chemistry</subject><subject>Aspirin - pharmacology</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Cell Division - drug effects</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Colonic Neoplasms - enzymology</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Cyclooxygenase 2</subject><subject>Cyclooxygenase 2 Inhibitors</subject><subject>Cyclooxygenase inhibitors</subject><subject>Cyclooxygenase Inhibitors - chemical synthesis</subject><subject>Cyclooxygenase Inhibitors - chemistry</subject><subject>Cyclooxygenase Inhibitors - pharmacology</subject><subject>Dinoprostone - biosynthesis</subject><subject>Drug Design</subject><subject>Enzyme inhibitors</subject><subject>Enzymes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Indomethacin - pharmacology</subject><subject>Inhibition</subject><subject>Inhibitory concentration 50</subject><subject>Innovations</subject><subject>Ions</subject><subject>Isoenzymes - chemistry</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Macrophages</subject><subject>Macrophages - enzymology</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Molecules</subject><subject>Mutagenesis, Site-Directed</subject><subject>Nonsteroidal anti-inflammatory agents</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostaglandin D2 - biosynthesis</subject><subject>Prostaglandin-Endoperoxide Synthases - chemistry</subject><subject>Prostaglandin-Endoperoxide Synthases - genetics</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Prostaglandins</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Sulfides</subject><subject>Sulfides - chemical synthesis</subject><subject>Sulfides - chemistry</subject><subject>Sulfides - pharmacology</subject><subject>Thromboxane B2 - biosynthesis</subject><subject>Tumor Cells, Cultured</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kUtv1DAUhS0EKkPhH1ApQhVsyOBH_MhyiHhUKuoG1pbjuRk8eOwhdqrOv8fRREViwepKPt-9OscHoSuC14RQ8SFZB8HCmiq85kzIdXlUT9CK4JbXLcXsKVphzEStsOTP0YuU9hgXrWUX6KIMwRVZoY-bdHSjC7V3v6D6Fj3YyUOq8k-Tqy7eGw8h-1N1E4zN7t5kqLqT9TE-nHYQTIKavkTPBuMTvFrmJfrx-dP37mt9e_flptvc1pYTmmtO8ZZwIsBwvjVAmBJ86KUVAwZiWiJp03PMZWMlt2aL20Ep0fdGEDvYvmXsEr073z2O8fcEKeuDSxa8NwHilLRsWCMUadpCvv0vSQQr6dV88s0_4D5OYygpNCWseMGMF-j9GdqVz9Au2BgyPGQbvYcd6JKxu9MbihVhDZMF52fcjjGlEQZ9HN3BjCdNsJ6b00tzujSn5-b03FzZu1q8TP0Bto9bS1VFv150k6zxw2iCdekRo0zippndvj5j-5Tj-FdWrcBSsD9OPqpF</recordid><startdate>19980522</startdate><enddate>19980522</enddate><creator>Kalgutkar, Amit S.</creator><creator>Crews, Brenda C.</creator><creator>Rowlinson, Scott W.</creator><creator>Garner, Carlos</creator><creator>Seibert, Karen</creator><creator>Marnett, Lawrence J.</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0-V</scope><scope>3V.</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9-</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0K</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope></search><sort><creationdate>19980522</creationdate><title>Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2</title><author>Kalgutkar, Amit S. ; Crews, Brenda C. ; Rowlinson, Scott W. ; Garner, Carlos ; Seibert, Karen ; Marnett, Lawrence J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-520d1516ea55dae13865fb7c6f0e1a91724b50574c75cad09f886bba61cfcb933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Acetylation</topic><topic>Acetylene - analogs & derivatives</topic><topic>Acetylene - chemical synthesis</topic><topic>Acetylene - chemistry</topic><topic>Acetylene - pharmacology</topic><topic>Alkynes</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Aspirin</topic><topic>Aspirin - chemistry</topic><topic>Aspirin - pharmacology</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Colonic Neoplasms - enzymology</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Cyclooxygenase 2</topic><topic>Cyclooxygenase 2 Inhibitors</topic><topic>Cyclooxygenase inhibitors</topic><topic>Cyclooxygenase Inhibitors - chemical synthesis</topic><topic>Cyclooxygenase Inhibitors - chemistry</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>Dinoprostone - biosynthesis</topic><topic>Drug Design</topic><topic>Enzyme inhibitors</topic><topic>Enzymes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Indomethacin - pharmacology</topic><topic>Inhibition</topic><topic>Inhibitory concentration 50</topic><topic>Innovations</topic><topic>Ions</topic><topic>Isoenzymes - chemistry</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Macrophages</topic><topic>Macrophages - enzymology</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>Molecules</topic><topic>Mutagenesis, Site-Directed</topic><topic>Nonsteroidal anti-inflammatory agents</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostaglandin D2 - biosynthesis</topic><topic>Prostaglandin-Endoperoxide Synthases - chemistry</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Prostaglandins</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Sulfides</topic><topic>Sulfides - chemical synthesis</topic><topic>Sulfides - chemistry</topic><topic>Sulfides - pharmacology</topic><topic>Thromboxane B2 - biosynthesis</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kalgutkar, Amit S.</creatorcontrib><creatorcontrib>Crews, Brenda C.</creatorcontrib><creatorcontrib>Rowlinson, Scott W.</creatorcontrib><creatorcontrib>Garner, Carlos</creatorcontrib><creatorcontrib>Seibert, Karen</creatorcontrib><creatorcontrib>Marnett, Lawrence J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Education Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Education Collection</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Agricultural Science Database</collection><collection>Education Database</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Education</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kalgutkar, Amit S.</au><au>Crews, Brenda C.</au><au>Rowlinson, Scott W.</au><au>Garner, Carlos</au><au>Seibert, Karen</au><au>Marnett, Lawrence J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1998-05-22</date><risdate>1998</risdate><volume>280</volume><issue>5367</issue><spage>1268</spage><epage>1270</epage><pages>1268-1270</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><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.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>9596581</pmid><doi>10.1126/science.280.5367.1268</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1998-05, Vol.280 (5367), p.1268-1270 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743468149 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Acetylation Acetylene - analogs & derivatives Acetylene - chemical synthesis Acetylene - chemistry Acetylene - pharmacology Alkynes Animals Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology Aspirin Aspirin - chemistry Aspirin - pharmacology Binding Sites Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cell Division - drug effects Cell growth Cell Line Colonic Neoplasms - enzymology Colonic Neoplasms - pathology Colorectal cancer Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase inhibitors Cyclooxygenase Inhibitors - chemical synthesis Cyclooxygenase Inhibitors - chemistry Cyclooxygenase Inhibitors - pharmacology Dinoprostone - biosynthesis Drug Design Enzyme inhibitors Enzymes Health aspects Humans Indomethacin - pharmacology Inhibition Inhibitory concentration 50 Innovations Ions Isoenzymes - chemistry Isoenzymes - genetics Isoenzymes - metabolism Macrophages Macrophages - enzymology Medical research Medical sciences Membrane Proteins Mice Molecules Mutagenesis, Site-Directed Nonsteroidal anti-inflammatory agents Nonsteroidal anti-inflammatory drugs Pharmacology. Drug treatments Prostaglandin D2 - biosynthesis Prostaglandin-Endoperoxide Synthases - chemistry Prostaglandin-Endoperoxide Synthases - genetics Prostaglandin-Endoperoxide Synthases - metabolism Prostaglandins Rats Rats, Inbred Lew Sulfides Sulfides - chemical synthesis Sulfides - chemistry Sulfides - pharmacology Thromboxane B2 - biosynthesis Tumor Cells, Cultured |
| title | Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T15%3A41%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aspirin-like%20Molecules%20that%20Covalently%20Inactivate%20Cyclooxygenase-2&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Kalgutkar,%20Amit%20S.&rft.date=1998-05-22&rft.volume=280&rft.issue=5367&rft.spage=1268&rft.epage=1270&rft.pages=1268-1270&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.280.5367.1268&rft_dat=%3Cgale_proqu%3EA20813437%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213574035&rft_id=info:pmid/9596581&rft_galeid=A20813437&rft_jstor_id=2896076&rfr_iscdi=true |