Pharmacological inhibition of LSD1 for cancer treatment

Guan Jun Yang; Pui Man Lei; Suk Yu Wong; Edmond Dik Lung MA; Chung Hang Leung

doi:10.3390/molecules23123194

Pharmacological inhibition of LSD1 for cancer treatment

Guan Jun Yang, Pui Man Lei, Suk Yu Wong, Edmond Dik Lung MA^*, Chung Hang Leung

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Review article › peer-review

83 Citations (Scopus)

Abstract

Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

Original language	English
Article number	3194
Journal	Molecules
Volume	23
Issue number	12
DOIs	https://doi.org/10.3390/molecules23123194
Publication status	Published - 4 Dec 2018

Scopus Subject Areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

User-Defined Keywords

Acute myeloid leukemia
Breast cancer
Cancer therapy
Demethylase
Histone
LSD1
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules23123194

Cite this

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title = "Pharmacological inhibition of LSD1 for cancer treatment",

abstract = "Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.",

keywords = "Acute myeloid leukemia, Breast cancer, Cancer therapy, Demethylase, Histone, LSD1, Prostate cancer",

author = "Yang, {Guan Jun} and Lei, {Pui Man} and Wong, {Suk Yu} and MA, {Edmond Dik Lung} and Leung, {Chung Hang}",

note = "Funding Information: Funding: This research is supported by Hong Kong Baptist University (FRG2/16-17/007, FRG2/17-18/003), the Health and Medical Research Fund (HMRF/14150561), the Research Grants Council (HKBU/12301115), the National Natural Science Foundation of China (21575121, 21775131, 21628502), the Hong Kong Baptist University Century Club Sponsorship Scheme 2018, the Interdisciplinary Research Matching Scheme (RC-IRMS/16-17/03), Interdisciplinary Research Clusters Matching Scheme (RC-IRCs/17-18/03), Innovation and Technology Fund (ITS/260/16FX), Collaborative Research Fund (C5026-16G), Matching Proof of Concept Fund (MPCF-001-2017/18), SKLEBA and HKBU Strategic Development Fund (SKLP_1718_P04), the Science and Technology Development Fund, Macao SAR (0072/2018/A2), the University of Macau (MYRG2016-00151-ICMS-QRCM and MYRG2018-00187-ICMS).",

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AU - Yang, Guan Jun

AU - Lei, Pui Man

AU - Wong, Suk Yu

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AU - Leung, Chung Hang

N1 - Funding Information: Funding: This research is supported by Hong Kong Baptist University (FRG2/16-17/007, FRG2/17-18/003), the Health and Medical Research Fund (HMRF/14150561), the Research Grants Council (HKBU/12301115), the National Natural Science Foundation of China (21575121, 21775131, 21628502), the Hong Kong Baptist University Century Club Sponsorship Scheme 2018, the Interdisciplinary Research Matching Scheme (RC-IRMS/16-17/03), Interdisciplinary Research Clusters Matching Scheme (RC-IRCs/17-18/03), Innovation and Technology Fund (ITS/260/16FX), Collaborative Research Fund (C5026-16G), Matching Proof of Concept Fund (MPCF-001-2017/18), SKLEBA and HKBU Strategic Development Fund (SKLP_1718_P04), the Science and Technology Development Fund, Macao SAR (0072/2018/A2), the University of Macau (MYRG2016-00151-ICMS-QRCM and MYRG2018-00187-ICMS).

PY - 2018/12/4

Y1 - 2018/12/4

N2 - Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

AB - Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

KW - Acute myeloid leukemia

KW - Breast cancer

KW - Cancer therapy

KW - Demethylase

KW - Histone

KW - LSD1

KW - Prostate cancer

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Pharmacological inhibition of LSD1 for cancer treatment

Abstract

Scopus Subject Areas

User-Defined Keywords

UN SDGs

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