Document Detail


Toxicological and metabolic considerations for histone deacetylase inhibitors.
MedLine Citation:
PMID:  23286281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Vorinostat and romidepsin were the first histone deacetylase (HDAC) inhibitors (HDi) that fulfilled the preclinical promise of anticancer potential in clinical trials. Nevertheless, they merely opened a new chapter in the history of cancer therapy. Demonstration of their antitumor activity was a straightforward task in in vitro setting. Proving their efficacy in vivo was much more difficult, since the effects of an administrated drug strongly depend on its absorption, distribution, metabolism and excretion.
AREAS COVERED: This article summarizes clinical data on the pharmacokinetic properties of HDi that are currently at more advanced stages of clinical development. Specific attention is paid to the metabolic pathways. Moreover, a comprehensive overview of HDi-related adverse effects is given.
EXPERT OPINION: At this moment, HDi form one of the most interesting classes of therapeutics, yet their efficacy and safety profiles could still be improved by i) designing better formulations, ii) more extensive characterization of their disposition at the preclinical stage, iii) targeting of individual disease-related deacetylase isoforms and/or their complexes, iv) selecting a target patient population with the highest probability of response based on molecular signatures.
Authors:
Joanna Fraczek; Tamara Vanhaecke; Vera Rogiers
Publication Detail:
Type:  Journal Article; Review     Date:  2013-01-04
Journal Detail:
Title:  Expert opinion on drug metabolism & toxicology     Volume:  9     ISSN:  1744-7607     ISO Abbreviation:  Expert Opin Drug Metab Toxicol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-09-25     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101228422     Medline TA:  Expert Opin Drug Metab Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  441-57     Citation Subset:  IM    
Affiliation:
VUB, Toxicology, Laarbeeklaan 103, Brussels 1090, Belgium. jfraczek@vub.ac.be
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MeSH Terms
Descriptor/Qualifier:
Benzamides / pharmacokinetics,  toxicity
Clinical Trials as Topic
Depsipeptides / pharmacokinetics,  toxicity
Dose-Response Relationship, Drug
Electrocardiography
Histone Deacetylase Inhibitors / pharmacokinetics*,  toxicity*
Humans
Hydroxamic Acids / pharmacokinetics,  toxicity
Pyridines / pharmacokinetics,  toxicity
Water-Electrolyte Balance
Chemical
Reg. No./Substance:
0/Benzamides; 0/Depsipeptides; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Pyridines; 0/entinostat; 128517-07-7/romidepsin; 149647-78-9/vorinostat

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


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