Epigenomic networking in drug development: from pathogenic mechanisms to pharmacogenomics

R Cacabelos - Drug development research, 2014 - Wiley Online Library
R Cacabelos
Drug development research, 2014Wiley Online Library
Abstract Preclinical Research Different 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 …
Abstract
Preclinical Research
Different 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.
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