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Epigenomic Networking in Drug Development: From Pathogenic Mechanisms to Pharmacogenomics
Author(s) -
Cacabelos Ramón
Publication year - 2014
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21219
Subject(s) - epigenomics , epigenetics , histone deacetylase , biology , histone , chromatin remodeling , dna methylation , histone deacetylase 5 , sirtuin , histone deacetylase 2 , cancer epigenetics , vorinostat , histone methyltransferase , cancer research , acetylation , genetics , gene expression , dna , gene
Preclinical ResearchDifferent epigenetic alterations ( DNA methylation, histone modifications, chromatin remodeling, noncoding RNA dysregulation) are associated with the phenotypic expression of complex disorders in which genomic, epigenomic, proteomic, and metabolomic changes, in conjunction with environmental factors, are involved. As epigenetic modifications are reversible and can be potentially targeted by pharmacological and dietary interventions, a series of epigenetic drugs have been developed, including DNA methyltransferase inhibitors (nucleoside analogs, small molecules, bioproducts, antisense oligonucleotides, miRNAs ), histone deacetylase inhibitors (short‐chain fatty acids, hydroxamic acids, cyclic peptides, benzamides, ketones, sirtuin inhibitors, sirtuin activators), histone acetyltransferase modulators, histone methyltransferase inhibitors, histone demethylase inhibitors, and noncoding RNAs ( miRNAs ), with potential effects against myelodysplastic syndromes, different types of cancer, and neurodegenerative disorders. Pharmacogenetic and pharmacoepigenetic studies are required for the proper evaluation of efficacy and safety issues in clinical trials with epigenetic drugs.