title: Multitarget Drugs: an Epigenetic Epiphany.
abstract: Epigenetics refers to changes in a biological phenotype that are not due to an underlying change in genotype. In eukaryotes, epigenetics involves a set of chemical modifications of the DNA and the histone proteins in nucleosomes. These dynamic changes are carried out by enzymes and modulate protein-protein and protein-nucleic acid interactions to determine whether specific genes are expressed or silenced. Both the epigenetic enzymes and recognition domains are currently important drug discovery targets, particularly for the treatment of cancer. This review summarizes the progress of epigenetic targets that have reached a clinical stage: DNA methyltransferases, histone deacetylases, lysine methyltransferases, lysine demethylases, and bromodomains; this is followed by a comprehensive survey of multitarget drugs that have included an epigenetic target as one of their mechanisms of action.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. a.ganesan@uea.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
mesh_terms: D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D057890:Epigenomics; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D004364:Pharmaceutical Preparations; D047428:Protein Kinase Inhibitors; D004248:DNA (Cytosine-5-)-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases
keywords: cancer; dual inhibitors; epigenetics; histone deacetylases; multitarget drugs