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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1995-10-12
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pubmed:abstractText |
A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A2 (hnps-PLA2) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA2 complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The application of structure-based drug design has made possible improvements in the binding of this screening lead to the enzyme by nearly three orders of magnitude. Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA2.
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pubmed:commentsCorrections |
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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 |
Jun
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pubmed:issn |
1072-8368
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
458-65
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7664108-Animals,
pubmed-meshheading:7664108-Binding Sites,
pubmed-meshheading:7664108-Biological Assay,
pubmed-meshheading:7664108-Calcium,
pubmed-meshheading:7664108-Crystallography, X-Ray,
pubmed-meshheading:7664108-Drug Design,
pubmed-meshheading:7664108-Guinea Pigs,
pubmed-meshheading:7664108-Humans,
pubmed-meshheading:7664108-Indoles,
pubmed-meshheading:7664108-Inflammation,
pubmed-meshheading:7664108-Kinetics,
pubmed-meshheading:7664108-Lung,
pubmed-meshheading:7664108-Models, Molecular,
pubmed-meshheading:7664108-Molecular Structure,
pubmed-meshheading:7664108-Phospholipases A,
pubmed-meshheading:7664108-Phospholipases A2,
pubmed-meshheading:7664108-Potassium Chloride,
pubmed-meshheading:7664108-Protein Conformation,
pubmed-meshheading:7664108-Structure-Activity Relationship
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pubmed:year |
1995
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pubmed:articleTitle |
Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2.
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pubmed:affiliation |
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
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pubmed:publicationType |
Journal Article
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