Top ▲

lysine demethylase 1A

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2669

Nomenclature: lysine demethylase 1A

Family: 1.14.11.- Histone demethylases

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
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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 6
pIC50 >7.7 (IC50 <2x10-8 M) [6]
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 3
pIC50 9.5 (IC50 3x10-10 M) [3]
GSK-LSD1 Small molecule or natural product Primary target of this compound Hs Inhibition 7.8 pIC50 10
pIC50 7.8 (IC50 1.6x10-8 M) [10]
OG-L002 Small molecule or natural product Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 2x10-8 M) [5]
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 8
pIC50 6.2 – 7.0 (IC50 7x10-7 – 1x10-7 M) [8]
Description: values.
GSK2879552 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 2
pIC50 6.4 [2]
NCL-1 Small molecule or natural product Hs Inhibition 5.8 pIC50 9
pIC50 5.8 (IC50 1.6x10-6 M) [9]
tranylcypromine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.4 pIC50 5
pIC50 4.4 (IC50 3.966x10-5 M) [5]
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 [9].
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0033184 positive regulation of histone ubiquitination IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0010725 regulation of primitive erythrocyte differentiation IMP
GO:0045648 positive regulation of erythrocyte differentiation IMP
GO:0045654 positive regulation of megakaryocyte differentiation IMP
Immuno Process:  Immune system development
GO Annotations:  Associated to 4 GO processes
GO:0010725 regulation of primitive erythrocyte differentiation IMP
GO:0030851 granulocyte differentiation IMP
GO:0045648 positive regulation of erythrocyte differentiation IMP
GO:0045654 positive regulation of megakaryocyte differentiation IMP
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:  1,4,7,11

References

Show »

1. 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]

2. 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.

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. SGC. GSK-LSD1 - a chemical probe for LSD1. Accessed on 03/03/2015. Modified on 03/03/2015. thegsk.org, http://www.thesgc.org/chemical-probes/LSD1

11. 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 14/10/2020. Accessed on 11/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2669.