Assays for histone deacetylases.
Epigenetics is defined as heritable changes in gene expression, i.e. the presentation of a certain phenotype, without alterations to the genetic code. This is a central phenomenon in developmental biology but also for the pathogenesis of a variety of diseases, e.g. for cancer in the case of silencing of tumor suppressor proteins. Reversible histone acetylation is an important player within the epigenetic machinery and histone deacetylases are the best studied epigenetic target for drug discovery. A first drug (vorinostat) is already approved for human cancer treatment. The strategies and protocols for monitoring histone deacetylase (HDAC) activity are an integral part of drug discovery approaches towards new HDAC inhibitors and will be reviewed in this article. The main focus is on biochemical in-vitro assays but cellular hit validation models are also presented.
Hauser
Alexander-Thomas
AT
Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany.
Jung
Mira
M
Jung
Manfred
M
D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors