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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2011-5-9
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pubmed:abstractText |
Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.
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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 |
May
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pubmed:issn |
1464-3391
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pubmed:author |
pubmed-author:BengtssonChristofferC,
pubmed-author:BlahoStefanS,
pubmed-author:BrickmannKayK,
pubmed-author:BroddefalkJohanJ,
pubmed-author:DavidssonOjvindO,
pubmed-author:DrmotaTomasT,
pubmed-author:FolmerRutgerR,
pubmed-author:HallénStefanS,
pubmed-author:HallbergKenthK,
pubmed-author:HovlandRagnarR,
pubmed-author:IsinEmreE,
pubmed-author:JohannessonPetraP,
pubmed-author:LöfgrenLarsL,
pubmed-author:LarssonLars-OlofLO,
pubmed-author:NilssonKristina EKE,
pubmed-author:NoeskeTobiasT,
pubmed-author:OakesNickN,
pubmed-author:OsterLindaL,
pubmed-author:PlowrightAlleyn TAT,
pubmed-author:SörmePernillaP,
pubmed-author:SaittonDavid BlombergDB,
pubmed-author:SchneckeVolkerV,
pubmed-author:StåhlbergPernillaP,
pubmed-author:WanHongH,
pubmed-author:WellnerEricE,
pubmed-author:Winkler MohrenfelsCC
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3039-53
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pubmed:meshHeading |
pubmed-meshheading:21515056-Acetyl-CoA Carboxylase,
pubmed-meshheading:21515056-Animals,
pubmed-meshheading:21515056-Crystallography, X-Ray,
pubmed-meshheading:21515056-Diabetes Mellitus, Type 2,
pubmed-meshheading:21515056-Drug Design,
pubmed-meshheading:21515056-Enzyme Inhibitors,
pubmed-meshheading:21515056-Fatty Acids,
pubmed-meshheading:21515056-Humans,
pubmed-meshheading:21515056-Liver,
pubmed-meshheading:21515056-Male,
pubmed-meshheading:21515056-Malonyl Coenzyme A,
pubmed-meshheading:21515056-Mice,
pubmed-meshheading:21515056-Mice, Inbred C57BL,
pubmed-meshheading:21515056-Models, Molecular,
pubmed-meshheading:21515056-Obesity,
pubmed-meshheading:21515056-Rats,
pubmed-meshheading:21515056-Rats, Zucker,
pubmed-meshheading:21515056-Small Molecule Libraries,
pubmed-meshheading:21515056-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats.
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pubmed:affiliation |
AstraZeneca Research and Development, Mölndal, Sweden.
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pubmed:publicationType |
Journal Article
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