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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2007-6-7
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pubmed:abstractText |
High-throughput screening of a subset of the J&J compound library containing the carboxylic acid functional group uncovered a bromophenyl derivative as a moderate potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the discovery of a novel series of GPR40 agonists with submicromolar potency. Among them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40 ligand linolenic acid in a functional Ca+2 flux assay in HEK cells expressing GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic beta-cell line. Our data supports the hypothesis that GPR40 may play an important role in fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited good pharmacokinetic profile in rat and may serve as a good candidate for in vivo study and may help to determine if GPR40 agonists would be beneficial in the treatment of type II diabetes.
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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 |
0022-2623
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pubmed:author |
pubmed-author:BaumannChrisC,
pubmed-author:DemarestKeith TKT,
pubmed-author:GunnetJoeJ,
pubmed-author:KuoGee-HongGH,
pubmed-author:LenhardJimJ,
pubmed-author:LiangYinY,
pubmed-author:LuSongfengS,
pubmed-author:MurrayWilliam VWV,
pubmed-author:ProostJefJ,
pubmed-author:SongFengbinF,
pubmed-author:WinesPamP,
pubmed-author:XuJun ZJZ
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2807-17
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17500511-Animals,
pubmed-meshheading:17500511-Biological Availability,
pubmed-meshheading:17500511-Calcium,
pubmed-meshheading:17500511-Cell Line,
pubmed-meshheading:17500511-Humans,
pubmed-meshheading:17500511-Hypoglycemic Agents,
pubmed-meshheading:17500511-Insulin,
pubmed-meshheading:17500511-Insulin-Secreting Cells,
pubmed-meshheading:17500511-Mice,
pubmed-meshheading:17500511-Phenylpropionates,
pubmed-meshheading:17500511-Propionic Acids,
pubmed-meshheading:17500511-Rats,
pubmed-meshheading:17500511-Receptors, G-Protein-Coupled,
pubmed-meshheading:17500511-Stereoisomerism,
pubmed-meshheading:17500511-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists.
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pubmed:affiliation |
Drug Discovery Division, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, New Jersey 08512, USA.
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pubmed:publicationType |
Journal Article
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