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The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors
Author(s) -
Spannhoff Astrid,
Hauser AlexanderThomas,
Heinke Ralf,
Sippl Wolfgang,
Jung Manfred
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900301
Subject(s) - demethylase , epigenetics , histone , histone methyltransferase , histone methylation , biology , epigenomics , methyltransferase , cancer epigenetics , dna methylation , genetics , computational biology , methylation , dna , gene expression , gene
Epigenetics is defined as heritable changes to the transcriptome that are independent of changes in the genome. The biochemical modifications that govern epigenetics are DNA methylation and posttranslational histone modifications. Among the histone modifications, acetylation and deacetylation are well characterized, whereas the fields of histone methylation and especially demethylation are still in their infancy. This is particularly true with regard to drug discovery. There is strong evidence that these modifications play an important role in the maintenance of transcription as well as in the development of certain diseases. This article gives an overview of the mechanisms of action of histone methyltransferases and demethylases, their role in the formation of certain diseases, and available inhibitors. Special emphasis is placed on the strategies that led to the first inhibitors which are currently available and the screening approaches that were used in that process.