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lysine demethylase 1A

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Target not currently curated in GtoImmuPdb

Target id: 2669

Nomenclature: lysine demethylase 1A

Family: 1.14.11.- Histone demethylases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 852 1p36.12 KDM1A lysine demethylase 1A
Mouse - 853 4 68.8 cM Kdm1a lysine (K)-specific demethylase 1A
Rat - 872 5q36 Kdm1a lysine demethylase 1A
Previous and Unofficial Names Click here for help
AOF2 | KDM1 | LSD1 | lysine (K)-specific demethylase 1A
Database Links Click here for help
Alphafold O60341 (Hs), Q6ZQ88 (Mm)
CATH/Gene3D 1.10.10.10, 3.50.50.60
ChEMBL Target CHEMBL6136 (Hs), CHEMBL4295874 (Mm)
Ensembl Gene ENSG00000004487 (Hs), ENSMUSG00000036940 (Mm), ENSRNOG00000022372 (Rn)
Entrez Gene 23028 (Hs), 99982 (Mm), 500569 (Rn)
Human Protein Atlas ENSG00000004487 (Hs)
KEGG Gene hsa:23028 (Hs), mmu:99982 (Mm), rno:500569 (Rn)
OMIM 609132 (Hs)
Pharos O60341 (Hs)
RefSeq Nucleotide NM_001009999 (Hs), NM_133872 (Mm), NM_001130098 (Rn)
RefSeq Protein NP_001009999 (Hs), NP_598633 (Mm), NP_001123570 (Rn)
UniProtKB O60341 (Hs), Q6ZQ88 (Mm)
Wikipedia KDM1A (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ORY-1001 Small molecule or natural product Primary target of this compound Hs Activation >7.7 pIC50 7
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [7]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CC-90011 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.5 pIC50 4
⤷ pIC50 9.5 (IC50 3x10-10 M) [4]
TAK-418 Small molecule or natural product Hs Inhibition 8.5 pIC50 1
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [1]
GSK-LSD1 Small molecule or natural product Primary target of this compound Hs Inhibition 7.8 pIC50 11
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [11]
OG-L002 Small molecule or natural product Hs Inhibition 7.7 pIC50 6
⤷ pIC50 7.7 (IC50 2x10-8 M) [6]
Description: In vitro KDM1A demethylation assay using purified human KDM1A protein and dimethylated H3K4 peptide as substrate.
RN-1 Small molecule or natural product Primary target of this compound Hs Inhibition 6.2 – 7.0 pIC50 9
⤷ pIC50 6.2 – 7.0 (IC50 7x10-7 – 1x10-7 M) [9]
Description: values.
GSK2879552 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 3
⤷ pIC50 6.4 [3]
NCL-1 Small molecule or natural product Hs Inhibition 5.8 pIC50 10
⤷ pIC50 5.8 (IC50 1.6x10-6 M) [10]
tranylcypromine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.4 pIC50 6
⤷ pIC50 4.4 (IC50 3.966x10-5 M) [6]
Description: In vitro KDM1A demethylation assay using purified human KDM1A protein and dimethylated H3K4 peptide as substrate.
Inhibitor Comments
Note that NCL-1 used to generate the IC50 in the table above is the 1S, 2R optical isomer [10].
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Physiological Functions Click here for help
Acts as a transcriptional coactivator or corepressor by demethylating lysine 4 and/or lysine 9 of histone H3 ( (H3K4me and H3K9me respectively). Acts only as part of a transcriptional complex eg with RCOR1/CoREST.
Species:  Human
Tissue: 
References:  2,5,8,12

References

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1. Baba R, Matsuda S, Arakawa Y, Yamada R, Suzuki N, Ando T, Oki H, Igaki S, Daini M, Hattori Y et al.. (2021) LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models. Sci Adv, 7 (11). DOI: 10.1126/sciadv.aba1187 [PMID:33712455]

2. Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R. (2002) A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci USA, 99 (11): 7420-5. [PMID:12032298]

3. Johnson NW, Kasparec J, Miller WH, Rouse MB, Suarez D, Tian X. (2012) Cyclopropylamines as lsd1 inhibitors. Patent number: WO2012135113 A2. Assignee: Glaxosmithkline Llc. Priority date: 25/03/2011. Publication date: 04/10/2012.

4. Kanouni T, Severin C, Cho RW, Yuen N Y-Y, Xu J, Shi L, Del Rosario JR, Stansfield RK, Lawton LN, Hosfield D et al.. (2020) Discovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1). J Med Chem, [Online ahead of print]. DOI: 10.1021/acs.jmedchem.0c00978 [PMID:33034194]

5. Lee MG, Wynder C, Cooch N, Shiekhattar R. (2005) An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature, 437 (7057): 432-5. [PMID:16079794]

6. Liang Y, Quenelle D, Vogel JL, Mascaro C, Ortega A, Kristie TM. (2013) A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency. MBio, 4 (1): e00558-12. [PMID:23386436]

7. Maes T, Mascaró C, Ortega A, Lunardi S, Ciceri F, Somervaille TC, Buesa C. (2015) KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease. Epigenomics, 7 (4): 609-26. [PMID:26111032]

8. Metzger E, Wissmann M, Yin N, Müller JM, Schneider R, Peters AH, Günther T, Buettner R, Schüle R. (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature, 437 (7057): 436-9. [PMID:16079795]

9. Neelamegam R, Ricq EL, Malvaez M, Patnaik D, Norton S, Carlin SM, Hill IT, Wood MA, Haggarty SJ, Hooker JM. (2012) Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem Neurosci, 3 (2): 120-128. [PMID:22754608]

10. Ogasawara D, Suzuki T, Mino K, Ueda R, Khan MN, Matsubara T, Koseki K, Hasegawa M, Sasaki R, Nakagawa H et al.. (2011) Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor. Bioorg Med Chem, 19 (12): 3702-8. [PMID:21227703]

11. SGC. GSK-LSD1 - a chemical probe for LSD1. Accessed on 03/03/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/GSK-LSD1

12. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119 (7): 941-53. [PMID:15620353]

How to cite this page

1.14.11.- Histone demethylases: lysine demethylase 1A. Last modified on 20/04/2021. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2669.