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

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Chemical Epigenetics

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 33))

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.

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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

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  1. The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan

    Takayoshi Suzuki

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  1. Takayoshi Suzuki
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Correspondence to Takayoshi Suzuki .

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  1. Sapienza University of Rome, Rome, Italy

    Antonello Mai

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

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

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Suzuki, T. (2019). Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors. In: Mai, A. (eds) Chemical Epigenetics. Topics in Medicinal Chemistry, vol 33. Springer, Cham. https://doi.org/10.1007/7355_2019_74

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