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Novel Drugs Targeting the Epigenome

  • Epigenetics ( ATY Lau, Section Editor)
  • Published:
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Abstract

Epigenetic drug discovery has its beginning in the cancer research arena, focusing first on DNA methylation and histone deacetylation. There are currently two DNA methyltransferase (DNMT) inhibitors and four histone deacetylase (HDAC) inhibitors approved by the US Food and Drug Administration (FDA) during the past 13 years. Over the past few years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms have exploded, providing new insights into the role of epigenetic control in gene regulation and leading to the discovery of a variety of new and specific drug targets. Among them, epigenetic “reader”—bromodomain and extra-terminal protein (BET), “writers”—disruptor of telomeric silencing 1-like (DOT1L), enhancer of zeste homolog 2 (EZH2), and protein arginine methyltransferase 5 (PRMT5), and “erasers”—lysine-specific histone demethylase 1 (LSD1) as well as isocitrate dehydrogenase (IDH) attract greater attention due to the ongoing clinical trials. This article provides a brief overview of new drugs modulating the above epigenetic targets, including their indication, mechanism of action, and disclosed chemical structures. The trend of epigenetic drug approval in the following few years is expectable, at least partially, from current clinical trials summarized in this review.

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Abbreviations

AITL:

Angioimmunoblastic T-cell lymphoma

ALCL:

Anaplastic large cell lymphoma

AML:

Acute myeloid leukemia

ATRT:

Atypical teratoid rhabdoid tumor

BET:

Bromodomain and extra-terminal protein

BMS:

Bristol-Myers Squibb

BRD:

Bromodomain

CAD:

Coronary artery disease

CRPC:

Castration-resistant prostate cancer

CVD:

Cardiovascular disease

DLBCL:

Diffuse large B-cell lymphoma

DM:

Diabetes mellitus

DNMT:

DNA methyltransferase

DOT1L:

Disruptor of telomeric silencing 1-like

ER:

Estrogen receptor

EZH2:

Enhancer of zeste homolog 2

FDA:

Food and Drug Administration

GSK:

GlaxoSmithKline

HDAC:

Histone deacetylase

HMT:

Histone methyltransferase

IDH:

Isocitrate dehydrogenase

LSD1:

Lysine-specific histone demethylase 1

MCL:

Mantle cell lymphoma

MDS:

Myelodysplastic syndrome

MM:

Multiple myeloma

MRT:

Malignant rhabdoid tumor

NHL:

Non-Hodgkin lymphoma

NSCLC:

Non-small cell lung cancer

NMC:

NUT midline carcinoma

PRMT:

Protein arginine methyltransferase

RTK:

Rhabdoid tumors of the kidney

SCLC:

Small cell lung cancer

TNBC:

Triple-negative breast cancer

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Acknowledgements

This work was supported by the National Key R&D Program of China (grant 2016YFA0502304) and the National Natural Science Foundation of China (grants 81230076).

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  1. State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China

    Zhuo Chen & Honglin Li

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  1. Zhuo Chen
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  2. Honglin Li
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Correspondence to Honglin Li.

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This article is part of the Topical Collection on Epigenetics

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Chen, Z., Li, H. Novel Drugs Targeting the Epigenome. Curr Pharmacol Rep 3, 268–285 (2017). https://doi.org/10.1007/s40495-017-0100-7

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