KDM1/LSD1
KDM1A/LSD1 (lysine-specific demethylase 1A) is a flavin adenine dinucleotide (FAD)-dependent histone demethylase that catalyzes oxidative demethylation of histone H3K4me1/2 and H3K9me1/2, thereby regulating chromatin structure and transcriptional programs central to cell fate determination and differentiation[1][2]. Mechanistically, LSD1 functions within transcriptional corepressor and chromatin-remodeling complexes, where its demethylase activity modulates epigenetic gene regulation and contributes to the dynamic control of gene expression[2][3]. Through actions on both histone and non-histone substrates, LSD1 participates in multiple biological pathways involved in development, hematopoiesis, neuronal function, and cellular homeostasis[3][4]. In disease settings, aberrant LSD1 activity supports cancer progression by regulating gene-expression programs associated with adaptation to the tumor microenvironment, epithelial-mesenchymal transition (EMT), stemness, and differentiation states[4]. Experimental studies further demonstrate that pharmacological or genetic inhibition of LSD1 can suppress EMT-associated transcriptional programs and impede tumor progression in preclinical models[4]. Compared with related isoforms, the neuronal LSD1 isoform displays distinct substrate specificity, preferentially demethylating H3K9me2 rather than H3K4me2 and promoting transcriptional programs linked to neuronal differentiation, learning, and memory[4]. This functional divergence highlights isoform-specific biological roles that should be considered when interpreting mechanistic studies and therapeutic responses[4]. For experimental applications, LSD1 has emerged as a major epigenetic drug target, and multiple small-molecule inhibitors, including tranylcypromine-derived compounds and clinical-stage LSD1 inhibitors, are being evaluated for hematologic malignancies and solid tumors, supporting its utility in target-validation and translational research programs[4][5].
References:
- [1]. Burg JM, et al. Lysine-Specific Demethylase 1A (KDM1A/LSD1): Product Recognition and Kinetic Analysis of Full-Length Histones. Biochemistry. 2016 Mar 22;55(11):1652-62. [Content Brief]
- [2]. Perillo B, et al. LSD1: more than demethylation of histone lysine residues. Exp Mol Med. 2020 Dec;52(12):1936-1947. [Content Brief]
- [3]. Uniprotkb.
- [4]. Kim D, et al. Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases. J Biomed Sci. 2021 Jun 4;28(1):41. [Content Brief]
- [5]. Gill H. Lysine-Specific Demethylase 1 (LSD1/KDM1A) Inhibition as a Target for Disease Modification in Myelofibrosis. Cells. 2022 Jul 3;11(13):2107. doi: 10.3390/cells11132107. Erratum in: Cells. 2022 Dec 19;11(24):4126. doi: 10.3390/cells11244126. PMID: 35805191; PMCID: PMC9265913. et al. Lysine-Specific Demethylase 1 (LSD1/KDM1A) Inhibition as a Target for Disease Modification in Myelofibrosis. Cells. 2022 Jul 3;11(13):2107. [Content Brief]
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KDM1/LSD1 Related Products (98)
Related Products (98)
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Antibodies (1)
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T-448
0 ImagesT-448 is a specific, orally active, CNS-penetrant and irreversible inhibitor of lysine-specific demethylase 1 (LSD1, an H3K4 demethylase), with an IC50 of 22 nM. T-448 enhances H3K4 methylation in primary cultured rat neurons.
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Bomedemstat dihydrochloride
0 ImagesCat. No.: HY-109169CPurity: 99.55%Synonyms: IMG-7289 dihydrochlorideBomedemstat (IMG-7289) dihydrochloride is an orally active and irreversible lysine-specific demethylase 1 (LSD1) inhibitor. Bomedemstat dihydrochloride can increase H3K4 and H3K9 methylation, and then alter gene expression. Bomedemstat dihydrochloride shows anti-cancer activities, inhibits cancer cell proliferation and induces apoptosis.
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Arborinine
0 ImagesArborinine is a potent and orally activeLSD1 inhibitor. Arborinine increases the expression of H3K4me1/2, H3K9me1/2, E-cad protein and decreases the expression of UBE2O protein level. Arborinine induces cell cycle arrest at S phase. Arborinine shows antitumor activity .
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Pulrodemstat
0 ImagesSynonyms: CC-90011; LSD1-IN-7Pulrodemstat (CC-90011) is a potent, selective, reversible and orally active inhibitor of lysine specific demethylase-1 (LSD1) with an IC50 of 0.25 nM. Pulrodemstat is less enzymatic inhibition against LSD2, MAO-A, and MAO-B. Pulrodemstat induces acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells differentiation and has potent anticancer activity.
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T-3775440 hydrochloride
0 ImagesT-3775440 (hydrochloride) is an irreversible lysine-specific histone demethylase (LSD1) inhibitor with an IC50 value of 2.1 nM.
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INCB059872
0 ImagesINCB059872 is a potent, orally active, selective and irreversible Lysine-Specific Demethylase 1 (LSD1) inhibitor that achieves inhibitory activity through the formation of covalent FAD-adducts. INCB059872 can inhibit cell proliferation and induce cell differentiation by upregulating the expression of myeloid differentiation markers CD86 and CD11b. INCB059872 can be used for the research of myeloid leukemia.
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INCB059872 dihydrochloride
0 ImagesINCB059872 dihydrochloride is a potent, orally active, selective and irreversible Lysine-Specific Demethylase 1 (LSD1) inhibitor that achieves inhibitory activity through the formation of covalent FAD-adducts. INCB059872 dihydrochloride can inhibit cell proliferation and induce cell differentiation by upregulating the expression of myeloid differentiation markers CD86 and CD11b. INCB059872 dihydrochloride can be used for the research of myeloid leukemia.
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HDAC6-IN-3
0 ImagesHDAC6-IN-3 (Compound 14), an antiprostate cancer agent, is a potent, orally active HDAC6 inhibitor with IC50s ranging from 0.02-1.54 μM for HDAC1/2/3/6/8/10. HDAC6-IN-3 is also an effective MAO-A (IC50=0.79 μM) and LSD1 inhibitor. HDAC6-IN-3 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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CBB1007 trihydrochloride
0 ImagesCat. No.: HY-15313CCAS No.: 2070015-03-9CBB1007 trihydrochloride is a reversible and selective LSD1 inhibitor with an IC50 of 5.27 µM for human LSD1. CBB1007 trihydrochloride significantly blocks the demethylase activity of LSD1 on H3K4Me2 and H3K4Me. CBB1007 trihydrochloride shows selectivity for LSD1 over LSD2 or JARID1A, and induces differentiation-related genes in pluripotent cells. CBB1007 trihydrochloride is studied in non-pluripotent cancer research, targeting teratocarcinoma, embryonic carcinoma, and seminoma.
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LSD1-IN-30
0 ImagesLSD1-IN-30 (compound 3) is a potent inhibitor of lysine-specific demethylase 1 (LSD1), with the IC50 value of 0.291 μM.
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LSD1/HDAC-IN-2
0 ImagesLSD1/HDAC-IN-2 (Compound 20c) is the inhibitor for LSD and HDAC, that inhibits LSD1, HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with IC50s of 39.0, 1.4, 1.0, 1.3, 2.9 and 16.0 nM, respectively. LSD1/HDAC-IN-2 inhibits the proliferation of cancer cells, especially the colorectal cancer cells. LSD1/HDAC-IN-2 arrests the cell cycle at G2/M phase, inhibits cell migration, and induces apoptosis in HCT-116 and HT-29 cells. LSD1/HDAC-IN-2 exhibits antitumor efficacy in mouse model without significant toxicity.
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TAS1440
0 ImagesTAS1440 is an orally active LSD1/KDM1A inhibitor with a human IC50 of 4.8 nM. TAS1440 non-covalently binds to the histone H3-binding pocket of LSD1, inhibiting demethylase activity and disrupting repressive complexes with INSM1 and SMAD2. TAS1440 activates tumor-suppressive TGF-β and NOTCH signaling pathways via transcriptional reprogramming. TAS1440 can be used for the research of small cell lung cancer, specifically the SCLC-A subtype.
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LD-110
0 ImagesCat. No.: HY-178825LD-110 is a PROTAC degrader targeting LSD1 with a DC50 of 0.44-1.24 μM. LD-110 acts through the CRBN E3 ubiquitin ligase and the ubiquitin-proteasome system, leading to H3K4me2 accumulation. LD-110 induces apoptosis and inhibits the growth and survival of multiple esophageal squamous cell carcinoma (ESCC) cell lines. LD-110 inhibits tumor growth in the KYSE-150 xenograft model. LD-110 can be used in research related to esophageal squamous cell carcinoma.
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CBB1007 hydrochloride
0 ImagesCBB1007 hydrochloride is a reversible and selective LSD1 inhibitor with an IC50 of 5.27 µM for human LSD1. CBB1007 hydrochloride significantly blocks the demethylase activity of LSD1 on H3K4Me2 and H3K4Me. CBB1007 hydrochloride shows selectivity for LSD1 over LSD2 or JARID1A, and induces differentiation-related genes in pluripotent cells. CBB1007 hydrochloride is studied in non-pluripotent cancer research, targeting teratocarcinoma, embryonic carcinoma, and seminoma.
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CBB1007
0 ImagesCat. No.: HY-15313CAS No.: 1379573-92-8CBB1007 is a reversible and selective LSD1 inhibitor with an IC50 of 5.27 µM for human LSD1. CBB1007 significantly blocks the demethylase activity of LSD1 on H3K4Me2 and H3K4Me. CBB1007 shows selectivity for LSD1 over LSD2 or JARID1A, and induces differentiation-related genes in pluripotent cells. CBB1007 is studied in non-pluripotent cancer research, targeting teratocarcinoma, embryonic carcinoma, and seminoma.
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LSD1-IN-5
0 ImagesCat. No.: HY-100859CAS No.: 2035912-55-9LSD1-IN-5 (Compound 4e) is a potent and reversible inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 121 nM. LSD1-IN-5 increases dimethylated Lys4 of histone H3, shows no effect on expression of LSD1.
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LSD1-IN-6
0 ImagesCat. No.: HY-100860CAS No.: 2035912-43-5LSD1-IN-6 (Compound 4m) is a potent and reversible inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 123 nM. LSD1-IN-6 increases dimethylated Lys4 of histone H3, shows no effect on expression of LSD1.
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Pulrodemstat Methylbenzenesulfonate
0 ImagesCat. No.: HY-129388CAS No.: 2097523-57-2Synonyms: CC-90011 Methylbenzenesulfonate; LSD1-IN-7 MethylbenzenesulfonatePulrodemstat (CC-90011) Methylbenzenesulfonate is a potent, selective, reversible and orally active inhibitor of lysine specific demethylase-1 (LSD1) with an IC50 of 0.25 nM. Pulrodemstat Methylbenzenesulfonate is less enzymatic inhibition against LSD2, MAO-A, and MAO-B. Pulrodemstat Methylbenzenesulfonate induces acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells differentiation and has potent anticancer activity.
