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.
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.
Eur J Med Chem. 2019 Jan 1;161:131-140. doi: 10.1016/j.ejmech.2018.10.040. Epub 2018 Oct 17.
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.
赖氨酸去甲基化酶 5B（KDM5B）是 2007 年发现的一种组蛋白去甲基化酶，负责清除 H3K4me2/3 激活标记。它参与靶基因启动子周围的多个抑制性转录复合物，并对染色质结构发挥广泛的调节作用。到目前为止，越来越多的证据表明 KDM5B 具有致癌功能。由于 H3K4me2/3 残基代表活性转录基因的转录起始位点，并且 H3K4 的去甲基化与转录抑制有关，因此它可能参与抑制肿瘤抑制因子的表达。因此，KDM5B 被认为是癌症治疗的有前途的药物靶点，许多药物化学家正在借助高通量筛选、基于结构的药物设计和构效关系研究来设计和合成有效的、选择性的 KDM5B 抑制剂。本文综述了 KDM5B 的基本生化和生理功能及其在癌症中的作用机制，并对 KDM5B 抑制剂进行了全面概述。
