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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. Image 1 • KDM5B was overexpressed in many cancers and performd an efficient transcriptional regulation function. • KDM5B was found to be an oncogene and biomarker of many cancers. • KDM5B was associated with cancer immunotherapy and drug resistance. • The SAR studies and developmental strategies of diverse KDM5B inhibitors were discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC 50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation. [ABSTRACT FROM AUTHOR]