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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-21
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pubmed:abstractText |
A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model.
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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 |
Jan
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pubmed:issn |
1464-3405
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
726-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18060775-Animals,
pubmed-meshheading:18060775-Cell Line, Tumor,
pubmed-meshheading:18060775-Enzyme Inhibitors,
pubmed-meshheading:18060775-Histone Deacetylase 1,
pubmed-meshheading:18060775-Histone Deacetylase 2,
pubmed-meshheading:18060775-Histone Deacetylase Inhibitors,
pubmed-meshheading:18060775-Mice,
pubmed-meshheading:18060775-Repressor Proteins,
pubmed-meshheading:18060775-Structure-Activity Relationship,
pubmed-meshheading:18060775-Transplantation, Heterologous
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pubmed:year |
2008
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pubmed:articleTitle |
Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2).
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pubmed:affiliation |
Department of Drug Design and Optimization-Medicinal Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. David_Witter@Merck.com
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pubmed:publicationType |
Journal Article
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