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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-12-24
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pubmed:abstractText |
Novel 2-aminoanilide histone deacetylase (HDAC) inhibitors were designed to increase their contact with surface residues surrounding the HDAC active site compared to the contacts made by existing clinical 2-aminoanilides such as SNDX-275, MGCD0103, and Chidamide. Their HDAC selectivity was assessed using p21 and klf2 reporter gene assays in HeLa and A204 cells, respectively, which provide a cell-based readout for the inhibition of HDACs associated either with the p21 or klf2 promoter. A subset of the designed compounds selectively induced p21 over klf2 relative to the clinical reference compound SNDX-275. A representative lead compound from this subset had antiproliferative effects in cancer cells associated with induction of acetylated histone H4, endogenous p21, cell cycle arrest, and apoptosis. The p21- versus klf2-selective compounds described herein may provide a chemical starting point for developing clinically-differentiated HDAC inhibitors for cancer therapy.
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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/Aminopyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Anilides,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/KLF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-amino-5-fluorobenzyl)-4-(N-(pyr...,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-aminophenyl)-4-((4-pyridin-3-yl...,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:ChenLiL,
pubmed-author:DaiS JSJ,
pubmed-author:DeenS MSM,
pubmed-author:HeYunY,
pubmed-author:LaiWayneW,
pubmed-author:LuXianpingX,
pubmed-author:NingZhiqingZ,
pubmed-author:OsL OLO,
pubmed-author:PengZhenghongZ,
pubmed-author:ROYJ AJA,
pubmed-author:WoodJason GJG,
pubmed-author:XieChuanmingC,
pubmed-author:ZhangChaoC,
pubmed-author:ZhangNanN,
pubmed-author:ZhangWeixingW,
pubmed-author:ZhangXiongwenX,
pubmed-author:ZhangZhenshanZ
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
110-6
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pubmed:meshHeading |
pubmed-meshheading:21145737-Aminopyridines,
pubmed-meshheading:21145737-Anilides,
pubmed-meshheading:21145737-Antineoplastic Agents,
pubmed-meshheading:21145737-Benzamides,
pubmed-meshheading:21145737-Catalytic Domain,
pubmed-meshheading:21145737-Cell Line, Tumor,
pubmed-meshheading:21145737-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:21145737-Genes, Reporter,
pubmed-meshheading:21145737-Histone Deacetylase Inhibitors,
pubmed-meshheading:21145737-Histone Deacetylases,
pubmed-meshheading:21145737-Humans,
pubmed-meshheading:21145737-Kruppel-Like Transcription Factors,
pubmed-meshheading:21145737-Neoplasms,
pubmed-meshheading:21145737-Promoter Regions, Genetic,
pubmed-meshheading:21145737-Pyrimidines,
pubmed-meshheading:21145737-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Application of p21 and klf2 reporter gene assays to identify selective histone deacetylase inhibitors for cancer therapy.
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pubmed:affiliation |
Roche R&D Center China Ltd, 720 Cai Lun Road, Building 5, Pudong, Shanghai 201203, PR China. jason.wong@roche.com
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pubmed:publicationType |
Journal Article
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