Lysine demethylase (KDM)

Lysine demethylases (KDMs) are a diverse class of enzymes that regulate the epigenetic landscape by removing methyl groups from lysine residues on histone proteins [UniProt: P61106]. They are categorized into two primary families: the flavin adenine dinucleotide (FAD)-dependent amine oxidases, such as LSD1 (KDM1A), and the JmjC-domain-containing dioxygenases, which require alpha-ketoglutarate and Fe(II) as cofactors [PubMed: 28211543]. By modulating the methylation status of histones like H3K4 and H3K9, KDMs play a fundamental role in controlling chromatin structure and gene expression, thereby influencing cell differentiation and development [PubMed: 24316879]. Dysregulation of KDM activity is a hallmark of various cancers, where they often act as oncogenic drivers by silencing tumor suppressors or maintaining cells in an undifferentiated state [PubMed: 30104645]. Consequently, KDMs have become high-priority therapeutic targets, with several inhibitors like iadademstat and bomedemstat currently in clinical trials for treating acute myeloid leukemia and other malignancies [ClinicalTrials.gov: NCT02913443, NCT04374882].

Other names

Histone lysine demethylaseProtein lysine demethylaseKDMLSDLysine-specific demethylase

Inhibition of the enzymatic removal of methyl groups from lysine residues on histone tails, thereby modulating chromatin structure and gene transcription.