Linked Life Data

15715470

Source:http://linkedlifedata.com/resource/pubmed/id/15715470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-17
pubmed:abstractText
To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21(WAF1/CIP1) by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1019-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15715470-Acetylation, pubmed-meshheading:15715470-Antineoplastic Agents, pubmed-meshheading:15715470-Binding, Competitive, pubmed-meshheading:15715470-Binding Sites, pubmed-meshheading:15715470-Cell Cycle Proteins, pubmed-meshheading:15715470-Cell Line, Tumor, pubmed-meshheading:15715470-Cell Proliferation, pubmed-meshheading:15715470-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:15715470-Drug Screening Assays, Antitumor, pubmed-meshheading:15715470-Histone Deacetylase Inhibitors, pubmed-meshheading:15715470-Histone Deacetylases, pubmed-meshheading:15715470-Histones, pubmed-meshheading:15715470-Humans, pubmed-meshheading:15715470-Hydroxamic Acids, pubmed-meshheading:15715470-Models, Molecular, pubmed-meshheading:15715470-Structure-Activity Relationship, pubmed-meshheading:15715470-Thiazoles
pubmed:year
2005
pubmed:articleTitle
Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't