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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0205314,
umls-concept:C0268575,
umls-concept:C0679622,
umls-concept:C1054142,
umls-concept:C1257890,
umls-concept:C1333201,
umls-concept:C1515655,
umls-concept:C1533691
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pubmed:issue |
14
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pubmed:dateCreated |
2004-6-24
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pubmed:abstractText |
The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E(2) in cells, and demonstrate potent in vivo anti-inflammatory and analgesic activity.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Butyric Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Group IV Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Heptanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Octanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Pla2g4a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pla2g4a protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3615-28
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15214789-Amides,
pubmed-meshheading:15214789-Animals,
pubmed-meshheading:15214789-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:15214789-Butyric Acids,
pubmed-meshheading:15214789-Cell Line,
pubmed-meshheading:15214789-Edema,
pubmed-meshheading:15214789-Group IV Phospholipases A2,
pubmed-meshheading:15214789-Heptanoic Acids,
pubmed-meshheading:15214789-Macrophage Activation,
pubmed-meshheading:15214789-Mice,
pubmed-meshheading:15214789-Octanoic Acids,
pubmed-meshheading:15214789-Pain Measurement,
pubmed-meshheading:15214789-Phospholipases A,
pubmed-meshheading:15214789-Phospholipases A2,
pubmed-meshheading:15214789-Rats,
pubmed-meshheading:15214789-Rats, Inbred F344,
pubmed-meshheading:15214789-Stereoisomerism,
pubmed-meshheading:15214789-Structure-Activity Relationship
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pubmed:year |
2004
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pubmed:articleTitle |
Inhibition of group IVA cytosolic phospholipase A2 by novel 2-oxoamides in vitro, in cells, and in vivo.
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pubmed:affiliation |
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece. gkokotos@cc.uoa.gr
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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