Pharmacological inhibition of KDM5A for cancer treatment

Guan Jun Yang; Jia Wu; Liang Miao; Ming Hui Zhu; Qian Jin Zhou; Xin Jiang Lu; Jian Fei Lu; Chung-Hang Leung; Dik Lung Ma; Jiong Chen

doi:10.1016/j.ejmech.2021.113855

Pharmacological inhibition of KDM5A for cancer treatment

Guan Jun Yang, Jia Wu, Liang Miao, Ming Hui Zhu, Qian Jin Zhou, Xin Jiang Lu, Jian Fei Lu, Chung-Hang Leung^*, Dik Lung Ma^*, Jiong Chen^*

^*Corresponding author for this work

Department of Chemistry

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

28 Citations (Scopus)

Abstract

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A 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 KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

Original language	English
Article number	113855
Journal	European Journal of Medicinal Chemistry
Volume	226
DOIs	https://doi.org/10.1016/j.ejmech.2021.113855
Publication status	Published - 15 Dec 2021

Scopus Subject Areas

Pharmacology
Drug Discovery
Organic Chemistry

User-Defined Keywords

Cancer therapy
Drug resistance
Histone methylation
Lysine-specific demethylase 5A
Screening methods

UN SDGs

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

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10.1016/j.ejmech.2021.113855

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title = "Pharmacological inhibition of KDM5A for cancer treatment",

abstract = "Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A 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 KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.",

keywords = "Cancer therapy, Drug resistance, Histone methylation, Lysine-specific demethylase 5A, Screening methods",

author = "Yang, {Guan Jun} and Jia Wu and Liang Miao and Zhu, {Ming Hui} and Zhou, {Qian Jin} and Lu, {Xin Jiang} and Lu, {Jian Fei} and Chung-Hang Leung and Ma, {Dik Lung} and Jiong Chen",

note = "Funding Information: This study is supported by grants from the Natural Science Foundation of Zhejiang Province ( LZ18C190001 ), National Natural Science Foundation of China ( 31972821 ) and State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products ( 2010DS700124-ZZ2008 ), the Science and Technology Development Fund, Macau SAR (File no. 0072/2018/A2 and 0007/2020/A1 ), SKL-QRCM(UM)-2020-2022, and the University of Macau ( MYRG2019-00002-ICMS ). Publisher Copyright: {\textcopyright} 2021 Elsevier Masson SAS",

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doi = "10.1016/j.ejmech.2021.113855",

language = "English",

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AU - Yang, Guan Jun

AU - Wu, Jia

AU - Miao, Liang

AU - Zhu, Ming Hui

AU - Zhou, Qian Jin

AU - Lu, Xin Jiang

AU - Lu, Jian Fei

AU - Leung, Chung-Hang

AU - Ma, Dik Lung

AU - Chen, Jiong

N1 - Funding Information: This study is supported by grants from the Natural Science Foundation of Zhejiang Province ( LZ18C190001 ), National Natural Science Foundation of China ( 31972821 ) and State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products ( 2010DS700124-ZZ2008 ), the Science and Technology Development Fund, Macau SAR (File no. 0072/2018/A2 and 0007/2020/A1 ), SKL-QRCM(UM)-2020-2022, and the University of Macau ( MYRG2019-00002-ICMS ). Publisher Copyright: © 2021 Elsevier Masson SAS

PY - 2021/12/15

Y1 - 2021/12/15

N2 - Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A 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 KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

AB - Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A 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 KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

KW - Cancer therapy

KW - Drug resistance

KW - Histone methylation

KW - Lysine-specific demethylase 5A

KW - Screening methods

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DO - 10.1016/j.ejmech.2021.113855

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JO - European Journal of Medicinal Chemistry

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Pharmacological inhibition of KDM5A for cancer treatment

Abstract

Scopus Subject Areas

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