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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1999-5-24
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pubmed:abstractText |
Comparative computer modeling of the X-ray crystal structures of cyclooxygenase isoforms COX-1 and COX-2 has led to the design of COX-2 selectivity into the nonselective inhibitor flurbiprofen. The COX-2 modeling was based on a postulated binding mode for flurbiprofen and took advantage of a small alcove in the COX-2 active site created by different positions of the Leu384 sidechain between COX-1 and COX-2. The design hypothesis was tested by synthesis and biological assay of a series of flurbiprofen analogs, culminating in the discovery of several inhibitors having up to 78-fold selectivity for COX-2 over COX-1.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0960-894X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
307-12
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:10091674-Binding Sites,
pubmed-meshheading:10091674-Crystallography, X-Ray,
pubmed-meshheading:10091674-Cyclooxygenase 2,
pubmed-meshheading:10091674-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:10091674-Cyclooxygenase Inhibitors,
pubmed-meshheading:10091674-Drug Design,
pubmed-meshheading:10091674-Flurbiprofen,
pubmed-meshheading:10091674-Humans,
pubmed-meshheading:10091674-Isoenzymes,
pubmed-meshheading:10091674-Membrane Proteins,
pubmed-meshheading:10091674-Molecular Structure,
pubmed-meshheading:10091674-Prostaglandin-Endoperoxide Synthases
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pubmed:year |
1999
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pubmed:articleTitle |
Structure-based design of COX-2 selectivity into flurbiprofen.
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pubmed:affiliation |
Merck Frosst Canada Inc., Pointe-Claire-Dorval, Quebec, Canada.
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pubmed:publicationType |
Journal Article
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