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Histone demethylase inhibitors block the enzymes that remove methyl groups from lysine residues on histones. Lysine-specific demethylase 1 (LSD1) is a flavin-dependent amine oxidase that demethylates mono- and dimethylated lysine 4 of histone H3 (H3K4). The larger Jumonji C (JmjC) domain family uses iron and 2-oxoglutarate as cofactors, and some members also remove trimethyl marks. SP2509 and GSK2879552 are inhibitors of LSD1 used in chromatin and differentiation studies. GSK J1 targets two demethylases of lysine 27 on histone H3 (H3K27), Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed X-chromosome tetratricopeptide repeat protein (UTX). GSK-J4 is its cell-permeable ester, used for studies in intact cells. JIB-04 acts on several JmjC demethylases, and YUKA1 inhibits lysine-specific demethylase 5A (KDM5A).
