title: The emerging therapeutic potential of histone methyltransferase and demethylase inhibitors.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spannhoff
authors.forename: Alexander-Thomas
authors.initials: AT
authors.lastname: Hauser
authors.forename: Ralf
authors.initials: R
authors.lastname: Heinke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: D001120:Arginine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011499:Protein Processing, Post-Translational
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D001120:Arginine; D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine