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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INCB059872 TFA
0 ImagesCat. No.: HY-141677CCAS No.: 1802909-50-7INCB059872 TFA 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 TFA can inhibit cell proliferation and induce cell differentiation by upregulating the expression of myeloid differentiation markers CD86 and CD11b. INCB059872 TFA can be used for the research of myeloid leukemia.
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INCB059872 tosylate
0 ImagesCat. No.: HY-141677BCAS No.: 2081940-67-0INCB059872 tosylate 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 tosylate can inhibit cell proliferation and induce cell differentiation by upregulating the expression of myeloid differentiation markers CD86 and CD11b. INCB059872 tosylate can be used for the research of myeloid leukemia.
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S1427
0 ImagesCat. No.: HY-146380CAS No.: 2447061-40-5S1427 is a tranylcypromine-derived LSD1 inhibitor with the IC50 of 390 nM and Ki of 80 nM. S1427 exhibits desirable hERG channel inhibition and microsomal stability profiles. Inhibition of LSD1 partially reduces the proliferation of cancer cells.
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LSD1-IN-23
0 ImagesCat. No.: HY-152032CAS No.: 3033660-66-8LSD1-IN-23 is a competitive/non-competitive mixed inhibitor of lysine specific demethylase 1 (LSD1). LSD1-IN-23 has LSD1 inhibitory activity with an IC50 value of 0.58 μM. LSD1-IN-23 can be used for the research of neuroblastoma (NB).
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LSD1/2-IN-4
0 ImagesCat. No.: HY-151194CAS No.: 2821068-09-9LSD1/2-IN-4, a PCPA derivative, is an inhibitor of lysine-specific demethylase 1 (LSD1) and lysine-specific demethylase 2 (LSD2). LSD1/2-IN-4 inhibits LSD1 and LSD2 with Ki values of 0.11 μM and 130 μM, respectively. LSD1/2-IN-4 can be used for the research of several cancers including T-cell acute lymphoblastic leukemia (TALL).
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NCL1
0 ImagesCat. No.: HY-12645CAS No.: 1196119-03-5NCL1 is a phenylcyclopropylamine (PCPA)-based Lysine-specific demethylase 1 (LSD1) inhibitor. NCL1 selectively inhibits LSD1 in preference to LSD2, with IC50 values of 2.5 and 26 μM for LSD1 and LSD2, respectively.
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cis-4-Br-2,5-F2-PCPA
0 ImagesCat. No.: HY-151190CAS No.: 2821068-03-3Synonyms: S1024cis-4-Br-2,5-F2-PCPA (S1024) is a selective inhibitor of lysine-specific demethylase 1 (LSD1), with a Ki value of 94 nM instead of 8.4 μM for LSD2. There is aberrant expression of LSD1 in cancer stem cells, cis-4-Br-2,5-F2-PCPA inhibits LSD1 cell proliferation and by increasing the level of dimethylated histone H3 at K4 (H3K4) in CCRF-CEM cells.
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KDM1/CDK1-IN-1
0 ImagesCat. No.: HY-147901CAS No.: 2938990-92-0KDM1/CDK1-IN-1 (compound 4) is a potent KDM1 and CDK1 inhibitor, with IC50 values of 0.096 and 0.078 μM, respectively.KDM1/CDK1-IN-1 induces cell cycle arrest at G2/M phase and apoptosis in HOP-92 cells. KDM1/CDK1-IN-1 exhibits potent cytotoxic activity against the CCRF-CEM, HOP-92 and Hep-G2 cells, with IC50 values of 16.34, 3.45 and 7.79 μM, respectively.
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LSD1-IN-26
0 ImagesCat. No.: HY-149978CAS No.: 3041141-72-1LSD1-IN-26 (compound 12u) is a potent LSD1 inhibitor, with an IC50 of 25.3 nM. LSD1-IN-26 also inhibits MAO-A (IC50=1234.57 nM) and MAO-B (IC50=3819.27 nM). LSD1-IN-26 significantly induces apoptosis in MGC-803 cells. LSD1-IN-26 can be used for gastric cancer research.
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LSD1-IN-21
0 ImagesCat. No.: HY-147697LSD1-IN-21 (compound 5a) is a potent and BBB-penetrated LSD1 (Lysine specific demethylase-1) inhibitor, with an IC50 of 0.956 µM. LSD1-IN-21 significantly reduces the pro-inflammatory cytokine TNF-α. LSD1-IN-21 shows good anticancer and anti-inflammatory activity.
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LSD1-IN-48
0 ImagesCat. No.: HY-181781CAS No.: 3104325-26-7LSD1-IN-48 is a tranylcypromine-pyrimidine derivative and selective LSD1 inhibitor with a human IC50 of 7.87 nM. LSD1-IN-48 increases H3K4me1/2 histone methylation levels. LSD1-IN-48 induces apoptosis, upregulates CD86, downregulates SOX2 and CD44, inhibits proliferation in cancer cells. LSD1-IN-48 can be used for the research of acute myeloid leukemia.
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LSD1-IN-35
0 ImagesCat. No.: HY-168086CAS No.: 2992690-04-5LSD1-IN-35 (Compound Z-1) is a selective LSD1 Inhibitor (IC50: 108 nM). LSD1-IN-35 inhibits the demethylation on H3K4me1/2. LSD1-IN-35 is an immunomodulator. LSD1-IN-35 promotes response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuates the PD-1/PD-L1 interaction.
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LSD1-IN-18
0 ImagesCat. No.: HY-146283CAS No.: 2983011-61-4LSD1-IN-18 (compound 7) is a potent, non-covalent and selective LSD1 inhibitor, with Ki of 0.156 μM and KD of 0.075 μM, respectively. LSD1-IN-18 shows antiproliferative activity in THP-1 leukemia cells and MDA-MB-231 breast cancer cells, with IC50 (72 h) of 0.16 and 0.21 μM, respectively.
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LSD1-IN-25
0 ImagesCat. No.: HY-149968CAS No.: 2911585-60-7
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LSD1-IN-46
0 ImagesCat. No.: HY-179339CAS No.: 2982716-97-0LSD1-IN-46 is a potent and orally active Lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 of 0.082 μM. LSD1-IN-46 interrupts the β-catenin-mediated transcriptional program, thereby suppressing the stemness of gastric cancer cells. LSD1-IN-46 exhibits strong anti-tumor activity. LSD1-IN-46 can be used for the research of gastric cancer.
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LSD1-IN-22
0 ImagesCat. No.: HY-151191CAS No.: 2821068-05-5LSD1-IN-22 is a potent Lysine-specific demethylase 1 (LSD1) inhibitor with a Ki value of 98 nM. LSD1-IN-22 has anti-proliferative activity against certain cancer cells.
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LSD1-IN-39
0 ImagesCat. No.: HY-172170CAS No.: 3024554-34-2LSD1-IN-39 (Compound 14) is a reversible inhibitor for LSD1 with an IC50 of 0.18 μM. LSD1-IN-39 exhibits broad-spectrum anti-proliferative activity against cancer cells, inhibits the cell migration of HepG2 and inhibits the epithelial-mesenchymal transition. LSD1-IN-39 exhibits antitumor activity in mouse models.
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LSD1-IN-19
0 ImagesCat. No.: HY-146284CAS No.: 2983011-81-8LSD1-IN-19 (compound 29) is a potent, non-covalent and selective LSD1 inhibitor, with Ki of 0.108 μM and KD of 0.068 μM, respectively. LSD1-IN-19 shows antiproliferative activity in THP-1 leukemia cells and MDA-MB-231 breast cancer cells, with IC50 (72 h) of 0.17 and 0.40 μM, respectively.
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MC4455
0 ImagesCat. No.: HY-182891MC4455 is a LSD1/PRMT5 dual inhibitor. MC4455 inhibits the LSD1/CoREST and PRMT5/MEP50 complex with IC50 values of 0.104 μM and 0.014 μM. MC4455 covalently binds to LSD1’s FAD cofactor, stabilizes the LSD1/CoREST complex. MC4455 induces myeloid differentiation, alters transcriptomic profiles, drives alternative splicing changes, and impairs leukemic cell viability in AML cells. MC4455 can be used for the research of acute myeloid leukemia.
