Multitarget Drugs: an Epigenetic Epiphany

被引：59

作者：

Ganesan, A. ^{[1
]}

机构：

[1] Univ E Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England

来源：

CHEMMEDCHEM | 2016年 / 11卷 / 12期

关键词：

cancer; dual inhibitors; epigenetics; histone deacetylases; multitarget drugs; INOSINE MONOPHOSPHATE DEHYDROGENASE; HISTONE DEACETYLASE INHIBITORS; SMALL-MOLECULE INHIBITORS; BIOLOGICAL EVALUATION; DUAL INHIBITORS; HYDROXAMIC ACID; SELECTIVE INHIBITORS; POTENT INHIBITORS; ROMIDEPSIN FK228; TOPOISOMERASE-II;

D O I：

10.1002/cmdc.201500394

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1227 / 1241

页数：15

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