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Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors

  • Takayoshi SuzukiEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

Histone lysine methylation, one of the epigenetic mechanisms, plays a pivotal role in various biological events, including cell cycle progression, immune response, and signal transduction. Histone methylation is closely associated with the oncogenesis and proliferation of cancer cells, and its alteration has been identified in many cancer cells. In addition, histone methylation is involved in such non-cancerous diseases as globin disorders and neurological disorders. Several enzymes that control histone methylation have been identified, including lysine-specific histone demethylases 1/2 (LSD1/2). As LSD1/2 are involved in various diseases, their inhibitors are considered useful not only as a chemical tool for probing the biology of LSD1/2 but also as therapeutic agents. In this chapter, the biology, pharmacology, and inhibitors of LSD1/2 are presented, and the potential of LSD inhibitors as therapeutic agents is discussed.

Keywords

Demethylase Disease Epigenetics Histone Inhibitor Lysine Methylation 

Abbreviations

ADC

Antibody-drug conjugates

AML

Acute myelogenous leukemia

AR

Androgen receptor

ATRA

All-trans-retinoic acid

CNS

Central nervous system

DDS

Drug delivery systems

ERα

Estrogen receptor α

FAD

Flavin adenine dinucleotide

GSC

Glioma stem cells

HCF-1

Host cell factor-1

HSV

Herpes simplex virus

KDM

Lysine demethylase

KMT

Lysine methyltransferase

LSD

Lysine-specific histone demethylase

MAO

Monoamine oxidase

MDS

Myelodysplastic syndrome

NSCLC

Non-small cell lung cancer

PCPA

Phenylcyclopropylamine

PDC

PCPA-drug conjugate

SCLC

Small cell lung carcinoma

siRNA

Small interfering RNA

VZV

Varicella zoster virus

Notes

Compliance with Ethical Standards

Funding: This work was partially supported by the JST CREST program (T.S.; JPMJCR14L2).

Conflict of Interest: The author declares no conflict of interest.

Ethical Approval: Not applicable.

Informed Consent: Not applicable.

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© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.The Institute of Scientific and Industrial ResearchOsaka UniversityIbarakiJapan

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