Targeting histone demethylase KDM5B for cancer treatment

  • Eur J Med Chem. 2020 Dec 15;208:112760. doi: 10.1016/j.ejmech.2020.112760.
Yun-Dong Fu  1 ,  Ming-Jie Huang  1 ,  Jia-Wen Guo  1 ,  Ya-Zhen You  1 ,  Hong-Min Liu  2 ,  Li-Hua Huang  3 ,  Bin Yu  4
Affiliations
  • 1. Green Catalysis Center, And College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.
  • 2. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
  • 3. Green Catalysis Center, And College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: [email protected].
  • 4. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: [email protected].
PMID: 32883639 DOI: 10.1016/j.ejmech.2020.112760
Abstract

KDM5B (Lysine-Specific Demethylase 5B) erases the methyl group from H3K4me2/3, which performs wide regulatory effects on chromatin structure, and represses the transcriptional function of genes. KDM5B functions as an oncogene and associates with human cancers closely. Targeting KDM5B has been a promising direction for curing Cancer since the emergence of potent KDM5B inhibitor CPI-455. In this area, most reported KDM5B inhibitors are Fe (Ⅱ) chelators, which also compete with the cofactor 2-OG in the active pockets. Besides, Some KDM5B inhibitors have been identified through high throughput screening or biochemical screening. In this reviewing article, we summarized the pioneering progress in KDM5B to provide a comprehensive realization, including crystal structure, transcriptional regulation function, cancer-related functions, development of inhibitors, and SAR studies. We hope to provide a comprehensive overview of KDM5B and the development of KDM5B inhibitors.

Keywords
Cancer; Fe(2+); Inhibitors; KDM5B; Transcriptional repression.
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