Lysine-specific histone demethylase 1A (LSD1) (LSD1)

Lysine-specific histone demethylase 1A (LSD1), also known as KDM1A, is a flavin-adenine dinucleotide (FAD)-dependent amine oxidase that specifically removes methyl groups from mono- and dimethylated lysine 4 and lysine 9 of histone H3 (H3K4 and H3K9) [PMID: 15592458, 30866513]. It acts as a critical epigenetic regulator, functioning as either a transcriptional repressor or activator depending on its association with various protein complexes like CoREST or NuRD [PMID: 33613658, 36776984]. LSD1 is frequently overexpressed in a wide range of malignancies, including acute myeloid leukemia (AML) and small cell lung cancer (SCLC), where it promotes oncogenesis by blocking cellular differentiation and enhancing stemness [PMID: 30866513, 34093552]. Therapeutic strategies focus on small-molecule inhibitors that either covalently bind the FAD cofactor or reversibly block the substrate-binding site, often aiming to induce terminal differentiation in cancer cells [PMID: 36776984, 32190011]. Beyond its catalytic role, LSD1 also serves as a structural scaffold for transcriptional complexes, and its inhibition is being explored to enhance the efficacy of immunotherapies by increasing tumor immunogenicity [PMID: 34093552, 37415633]. Clinical trials are currently evaluating several LSD1 inhibitors, both as monotherapy and in combination with other agents like all-trans retinoic acid (ATRA) or checkpoint inhibitors [PMID: 36776984].

Other names

KDM1AKDM1AOF2BHC110KIAA0601

Irreversible or reversible inhibition of the FAD-dependent catalytic activity; disruption of scaffolding/non-catalytic functions (e.g., interaction with CoREST or GFI1B) [PMID: 36776984, 32190011].