Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target

Yi-Chao Zheng; Jiao Chang; Lin-Chen Wang; Hong-Mei Ren; Jing-Ru Pang; Hong-Min Liu

doi:10.1016/j.ejmech.2018.10.040

Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target

Eur J Med Chem. 2019 Jan 1:161:131-140. doi: 10.1016/j.ejmech.2018.10.040. Epub 2018 Oct 17.

Authors

Yi-Chao Zheng¹, Jiao Chang², Lin-Chen Wang², Hong-Mei Ren², Jing-Ru Pang², Hong-Min Liu³

Affiliations

¹ Zhengzhou Research Base, State Key Laboratory of Cotton Biology, Zhengzhou University, Zhengzhou, 450000, China; Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China; National Center for International Research of Micro-nano Molding Technology & Key Laboratory for Micro Molding Technology of Henan Province, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China; Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, 455000, China.
² Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
³ Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China. Electronic address: liuhm@zzu.edu.cn.

PMID: 30343192
DOI: 10.1016/j.ejmech.2018.10.040

Abstract

Lysine demethylase 5B (KDM5B) is a histone demethylase identified in 2007, which is responsible for erasing H3K4me2/3 activation marker. It participates in multiple repressive transcriptional complexes around target gene promoters and performs wide regulatory effects on chromatin structure. Until now, there is growing evidence for the oncogenic function of KDM5B. As the H3K4me2/3 residue represents the transcription initiation site of the active transcription gene, and demethylation of H3K4 is associated with transcriptional repression, making it a potential participant in inhibiting the expression of tumor suppressors. Therefore, KDM5B is considered as a promising drug target for cancer therapy, and many medicinal chemists are trying to design and synthesize potent and selective KDM5B inhibitors with the aid of high-throughput screening, structure based drug design, and structure activity relationship studies. This review focuses on the basic biochemical and physiological function of KDM5B and its involved mechanisms in cancers, a comprehensive overview of KDM5B inhibitors is also introduced.

Keywords: Cancer; Histone modification; Inhibitor; KDM5B.

Publication types

Review

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Drug Screening Assays, Antitumor
Humans
Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors*
Jumonji Domain-Containing Histone Demethylases / metabolism
Molecular Structure
Neoplasms / drug therapy*
Neoplasms / metabolism
Nuclear Proteins / antagonists & inhibitors*
Nuclear Proteins / metabolism
Repressor Proteins / antagonists & inhibitors*
Repressor Proteins / metabolism
Structure-Activity Relationship

Substances

Antineoplastic Agents
Nuclear Proteins
Repressor Proteins
Jumonji Domain-Containing Histone Demethylases
KDM5B protein, human