Source:http://linkedlifedata.com/resource/pubmed/id/18363352
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2008-4-17
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| pubmed:abstractText |
CB1 receptor antagonists have proven to be clinically effective in treating obesity and related disorders. We report here the identification of a novel class of azetidinone CB1 antagonists by using virtual screening methods. For this purpose, we developed a pharmacophore model based on known representative CB1 antagonists and employed it to screen a database of about a half million Schering-Plough compounds. We applied a stepwise filtering protocol based on molecular weight, compound availability, and a modified rule-of-five to reduce the number of hits. We then combined Bayesian modeling and clustering techniques to select a final set of 420 compounds for in vitro testing. Five compounds were found to have >50% inhibition at 100 nM in a CB1 competitive binding assay and were further characterized by using both CB1 and CB2 assays. The most potent compound has a CB1 K i of 53 nM and >5-fold selectivity against the CB2 receptor.
|
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0022-2623
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
24
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| pubmed:volume |
51
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2439-46
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| pubmed:meshHeading | |
| pubmed:year |
2008
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| pubmed:articleTitle |
Identification of novel cannabinoid CB1 receptor antagonists by using virtual screening with a pharmacophore model.
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| pubmed:affiliation |
Department of Structural Chemistry, CNS Biological Research, and CNS/CV Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. hongwu.wang@spcorp.com
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| pubmed:publicationType |
Journal Article
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