INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW
Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11
- This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee for epigenetic targets (chromatin-modifying enzymes and bromodomain-containing proteins), reviews our current understanding of their structure, pharmacology and functions, and their likely physiological roles in health and disease. More information on these families of targets can be found in the Concise Guide to PHARMACOLOGY (http://onlinelibrary.wiley.com/doi/10.1111/bph.12445/abstract) and for each member of the families in the corresponding database (http://www.guidetopharmacology.org/GRAC/ReceptorFamiliesForward?type=ENZYME&familyId=865; http://dev.guidetopharmacology.org/GRAC/ReceptorFamiliesForward?type=OTHER&familyId=866).
The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy.