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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 |
2005-3-17
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pubmed:abstractText |
Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-betaII (IC(50) = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.
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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/ERG1 potassium channel,
http://linkedlifedata.com/resource/pubmed/chemical/Ether-A-Go-Go Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Indazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:AddoMichael FMF,
pubmed-author:Andrade-GordonPatriciaP,
pubmed-author:CheungWai-ManWM,
pubmed-author:ConwayBruce RBR,
pubmed-author:CrollDianeD,
pubmed-author:DamianoBruce PBP,
pubmed-author:DemarestKeith TKT,
pubmed-author:DerianClaudia KCK,
pubmed-author:EckardtAnnette JAJ,
pubmed-author:EmanuelStuartS,
pubmed-author:HeckerLeonard RLR,
pubmed-author:LiJianJ,
pubmed-author:MaryanoffBruce EBE,
pubmed-author:McComseyDavid FDF,
pubmed-author:QuanLiL,
pubmed-author:SmithCharles ECE,
pubmed-author:WhiteKimberly BKB,
pubmed-author:YeHongH,
pubmed-author:ZhangHan-ChengHC
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1725-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15771419-Animals,
pubmed-meshheading:15771419-Cell Line,
pubmed-meshheading:15771419-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:15771419-Glycogen Synthase Kinase 3,
pubmed-meshheading:15771419-Guinea Pigs,
pubmed-meshheading:15771419-Humans,
pubmed-meshheading:15771419-Indazoles,
pubmed-meshheading:15771419-Indoles,
pubmed-meshheading:15771419-Interleukin-8,
pubmed-meshheading:15771419-Isoenzymes,
pubmed-meshheading:15771419-Long QT Syndrome,
pubmed-meshheading:15771419-Maleimides,
pubmed-meshheading:15771419-Models, Molecular,
pubmed-meshheading:15771419-Patch-Clamp Techniques,
pubmed-meshheading:15771419-Potassium Channel Blockers,
pubmed-meshheading:15771419-Potassium Channels, Voltage-Gated,
pubmed-meshheading:15771419-Protein Kinase C,
pubmed-meshheading:15771419-Structure-Activity Relationship
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pubmed:year |
2005
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pubmed:articleTitle |
Novel indolylindazolylmaleimides as inhibitors of protein kinase C-beta: synthesis, biological activity, and cardiovascular safety.
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pubmed:affiliation |
Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA. hzhang@prdus.jnj.com
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pubmed:publicationType |
Journal Article
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