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 free base
0 ImagesCat. No.: HY-122635CAS No.: 1597426-52-2T-448 free base 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 free base enhances H3K4 methylation in primary cultured rat neurons.
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LSD1/HDAC6-IN-1
0 ImagesCat. No.: HY-131970CAS No.: 2738306-38-0LSD1/HDAC6-IN-1 is an orally active dual inhibitor of lysine specific demethylase 1(LSD1)/Histone deacetylase 6 (HDAC6), with anti-tumor activity. LSD1/HDAC6-IN-1 can be used for the research of multiple myeloma (MM).
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LSD1-IN-13 hydrochloride
0 ImagesCat. No.: HY-144675ACAS No.: 2170347-90-5LSD1-IN-13 hydrochloride (compound 7e) is an orally active and potent LSD1 inhibitor, with an IC50 of 24.43 nM. LSD1-IN-13 hydrochloride can activate CD86 expression, with an EC50 of 470 nM. LSD1-IN-13 hydrochloride induces differentiation of AML (acute myeloid leukemia) cell lines.
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MC2652
0 ImagesCat. No.: HY-144755CAS No.: 2771425-46-6MC2652 (compound 1a) is a potent LSD1 inhibitor. MC2652 displays high inhibiting effects in MV4-11 and NB4 leukaemia cells. MC2652 shows antiproliferative activity against prostate cancer LNCaP cells.
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TAS1440 benzoate
0 ImagesCat. No.: HY-183067ACAS No.: 2642224-15-3TAS1440 benzoate is an orally active LSD1/KDM1A inhibitor with a human IC50 of 4.8 nM. TAS1440 benzoate non-covalently binds to the histone H3-binding pocket of LSD1, inhibiting demethylase activity and disrupting repressive complexes with INSM1 and SMAD2. TAS1440 benzoate activates tumor-suppressive TGF-β and NOTCH signaling pathways via transcriptional reprogramming. TAS1440 benzoate can be used for the research of small cell lung cancer, specifically the SCLC-A subtype.
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MC4491
0 ImagesCat. No.: HY-182892MC4491 is a selective LSD1/PRMT5 inhibitor, with an IC50 of 0.152 μM against the LSD1/CoREST complex and an IC50 of 0.043 μM against the PRMT5/MEP50 complex. MC4491 induces transcriptomic changes and splicing alterations in AML cells. MC4491 is applicable for the research of acute myeloid leukemia.
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LSD1-IN-31
0 ImagesCat. No.: HY-161849LSD1-IN-31 (compound 11e) can directly bind to LSD1/CoREST complex to reduce LSD1 demethylation enzymatic activity. LSD1-IN-31 inhibits LSD1 demethylation activity and influences its downstream IκB/NF-κB signaling pathway. LSD1-IN-31 inhibits osteoclastic bone loss in vitro and in vivo. LSD1-IN-31 can be used for osteoporosis research.
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LSD1-IN-17
0 ImagesCat. No.: HY-144758CAS No.: 3033060-70-4LSD1-IN-17 (compound 5b) is a potent LSD1 inhibitor. LSD1-IN-17 can inhibit LSD1-CoREST, MAO-A and MAO-B, with IC50 values of 0.005, 0.028, and 0.820 μM, respectively. LSD1-IN-17 displays cell growth arrest in prostate cancer LNCaP cells, with an IC50 of 17.2 μM.
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3β-Acetoxyl-atractylenolide I
0 ImagesCat. No.: HY-N18236CAS No.: 2538955-98-33β-Acetoxyl-atractylenolide I is a LSD1 inhibitor with an IC50 of 57 μM. 3β-Acetoxyl-atractylenolide I blocks tumor growth, metastasis and invasion. 3β-Acetoxyl-atractylenolide I is used in the research of various cancers including prostate cancer, breast cancer, neuroblastoma, gastric cancer, colon cancer, bladder cancer, esophageal cancer, acute myeloid leukemia and retinoblastoma.
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LSD1-IN-34
0 ImagesCat. No.: HY-162729CAS No.: 3048029-74-6LSD1-IN-34 (Compound 7d) is the orally active inhibitor for Lysine-specific demethylase (LSD) and monoamine oxidase (MAO), with IC50 of 4.51 and 18.46 nM, for LSD1 and MAO A. LSD1-IN-34 inhibits the Ang II-induced neonatal rat myocardial fibroblasts (NRCFs) activation, without significant toxicity (20 μM). LSD1-IN-34 inhibits TGFβ/Smad signaling pathway, and ameliorates heart failure in mice. LSD1-IN-34 exhibits good pharmacokinetic characteristics in rats.
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LSD1-IN-43
0 ImagesCat. No.: HY-176254LSD1-IN-43 is a highly selective, reversible, orally active and brain-penetrant LSD1 inhibitor with an IC50 value of 0.8 μM. LSD1-IN-43 has low inhibitory activity against MAO-A and MAO-B, two homologs of LSD1. LSD1-IN-43 significantly inhibits Aβ aggregation and enhances Aβ-induced neuronal cell viability. LSD1-IN-43 can be used for the study of Alzheimer’s disease (AD).
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HSP90/LSD1-IN-1
0 ImagesCat. No.: HY-169098CAS No.: 3102917-71-2HSP90/LSD1-IN-1 (compound 6) is a HSP90/LSD1 dual inhibitor. HSP90/LSD1-IN-1 inhibits the proliferation of prostate cancer cell lines PC-3 and DU145, with GI50 values of 0.24 and 0.30 μM, respectively.
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LSD1-IN-15
0 ImagesCat. No.: HY-144756CAS No.: 3033060-62-4LSD1-IN-15 (compound 1b) is a potent LSD1 inhibitor. LSD1-IN-15 can inhibit LSD1-CoREST, MAO-A and MAO-B, with IC50 values of 0.149, 0.028, and 0.327 μM, respectively. LSD1-IN-15 displays cell growth arrest in prostate cancer LNCaP cells, with an IC50 of 9.9 μM.
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NCD38
0 ImagesCat. No.: HY-183202CAS No.: 1456907-39-3NCD38 is a Lysine-specific demethylase 1 (LSD1) inhibitor with a target IC50 of 0.59 μM. NCD38 selectively disrupts LSD1-GFI1B interactions, dissociates LSD1 and CoREST from the ERG super-enhancer. NCD38 increases apoptosis-related protein levels, induces apoptosis and reduces SOX2 and Oct4 levels. NCD38 can be used for the research of acute myeloid leukemia.
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LSD1-IN-49
0 ImagesCat. No.: HY-186116CAS No.: 1422533-70-7LSD1-IN-49 is an irreversible LSD1/KDM1A inhibitor with an IC50 of 29 nM against hLSD1. LSD1-IN-49 irreversibly inhibits the enzymatic activity of LSD1 by forming an adduct with flavin adenine dinucleotide (FAD) in the binding pocket of LSD1. LSD1-IN-49 is applicable to research related to schizophrenia, autism spectrum disorder and Huntington's disease.
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DDP-38003
0 ImagesCat. No.: HY-19612CAS No.: 1831167-97-5DDP-38003 (Compound 15) is an orally active KDM1A/LSD1 inhibitor with an IC50 value of 84 nM. DDP-38003 exhibits anticancer activity against promyelocytic leukemia.
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LSD1-UM-109
0 ImagesCat. No.: HY-149595CAS No.: 2252446-26-5LSD1-UM-109 is a ighly potent and reversible LSD1 inhibitor with an IC50 of 3.1 nM. LSD1-UM-109 inhibits cell growth with IC50 values of 0.6 nM in the MV4;11 acute leukemia cell line and 1.1 nM in the H1417 small-cell lung cancer cell line.
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LSD1-IN-41
0 ImagesCat. No.: HY-172519CAS No.: 2295907-44-5
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TAK-418 free base
0 ImagesCat. No.: HY-138830BCAS No.: 1818252-52-6TAK-418 free base is an orally active, blood-brain barrier-penetrant LSD1 inhibitor with a human IC50 of 2.9 nM. TAK-418 free base irreversibly inhibits LSD1 by forming a compact flavin-FAD adduct with the catalytic domain FAD, blocking the demethylation of H3K4me1/2 and H3K9me1/2 without disrupting the LSD1-GFI1B interaction. TAK-418 free base restores normally dysregulated brain gene expression and DNA methylation, increases H3K4me1/2/3 and H3K9me2 at the Ucp2 locus, and induces Ucp2 mRNA expression. TAK-418 free base rescues defective H3K4 histone modifications, normalizes adult neurogenesis, and improves recognition memory, social behavior, and cognition in rodent models. TAK-418 free base can be used in research related to neurodevelopmental disorders, Alzheimer's disease, and autism spectrum disorders.
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LSD1-IN-38
0 ImagesCat. No.: HY-170403LSD1-IN-38 (Compound 23e) is a reversible, orally active inhibitor for lysine specific demethylase 1 (LSD1) with an IC50 of 1.2 nM. LSD1-IN-38 inhibits the proliferation of cancer cells MV4-11, Kasumi-1 and NCI-H526, with IC50 of 5, 4 and 11 nM, respectively. LSD1-IN-38 activates CD86 expression with an EC50 of 0.034 μM, and induces differentiation in MV4−11 cell. LSD1-IN-38 exhibits antitumor efficacy in mouse models.
