Document Detail


Non-hydroxamate histone deacetylase inhibitors.
MedLine Citation:
PMID:  16305476     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of histone deacetylase (HDAC) inhibitors have been developed as anticancer agents and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA), Trichostatin A (TSA) and NVP-LAQ824. However, hydroxamic acids have been associated with poor pharmacokinetics and severe toxicity. In addition, although isozyme-selective HDAC inhibitors are considered useful not only as tools for probing the biology of an enzyme but as drugs with low toxicity, many of the hydroxamate HDAC inhibitors do not distinguish well among the HDAC isozymes. Thus, there has been considerable interest in developing non-hydroxamate HDAC inhibitors. To date, small fatty acids, o-aminoanilides, electrophilic ketones, N-formyl hydroxylamines, thiols and mercaptoamides have been reported as non-hydroxamate HDAC inhibitors, and some of them show antiproliferative activity comparable to hydroxamates. Interestingly, hydroxamate HDAC inhibitors such as SAHA and TSA do not discriminate well among the HDAC isozymes whereas many non-hydroxamate HDAC inhibitors have shown selectivity. These non-hydroxamate HDAC inhibitors should pave the way for the development of tools for biological research and new medicines with few side effects. In this review, we introduce non-hydroxamate HDAC inhibitors describing their design, enzyme inhibition, cancer cell growth inhibition and isozyme selectivity.
Authors:
Takayoshi Suzuki; Naoki Miyata
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current medicinal chemistry     Volume:  12     ISSN:  0929-8673     ISO Abbreviation:  Curr. Med. Chem.     Publication Date:  2005  
Date Detail:
Created Date:  2005-11-24     Completed Date:  2006-08-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9440157     Medline TA:  Curr Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2867-80     Citation Subset:  IM    
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
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Design
Enzyme Inhibitors / chemical synthesis*,  chemistry,  pharmacology
Histone Deacetylase Inhibitors*
Humans
Inhibitory Concentration 50
Molecular Structure
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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