Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNR0UQ)

DTT Name Lysine-specific histone demethylase 1 (LSD)
Synonyms Lysine-specific histone demethylase 1A; LSD1; KIAA0601; KDM1; Flavin-containing amine oxidase domain-containing protein 2; BRAF35-HDAC complex protein BHC110; AOF2
Gene Name KDM1A
DTT Type
Clinical trial target
 [1]
BioChemical Class
CH-NH(2) donor oxidoreductase
UniProt ID
KDM1A_HUMAN
TTD ID
T16739
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 1.-.-.-
Sequence
MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTP
RKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEY
REMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEGAAFQ
SRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEA
PYNSDTVLVHRVHSYLERHGLINFGIYKRIKPLPTKKTGKVIIIGSGVSGLAAARQLQSF
GMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKC
PLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQE
KHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLV
KSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFAN
ATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGC
EVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLN
KVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISD
DVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPI
TPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQA
TPGVPAQQSPSM
Function
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.
KEGG Pathway
Thermogenesis (hsa04714 )
Reactome Pathway
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
HDACs deacetylate histones (R-HSA-3214815 )
BioCyc Pathway
MetaCyc:ENSG00000004487-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
8 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CC-90011 DM0EDHJ Lymphoma 2A80-2A86 Phase 2 [1]
IMG-7289 DML9AVG Acute myeloid leukaemia 2A60 Phase 2 [1]
ORY-2001 DMYM0UY Alzheimer disease 8A20 Phase 2 [2]
Vafidemstat DM64ZGY Alzheimer disease 8A20 Phase 2 [3]
INCB59872 DMRLV7G Acute myeloid leukaemia 2A60 Phase 1/2 [1]
GSK2879552 DMT3V2W Small-cell lung cancer 2C25.Y Phase 1 [4]
Seclidemstat DMCP7SD Ewing sarcoma 2B52 Phase 1 [5]
TAS-1440 DMHIA7Y Acute myeloid leukaemia 2A60 Phase 1 [6]
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⏷ Show the Full List of 8 Clinical Trial Drug(s)
69 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aryl cyclopropylamine derivative 3 DMZECH7 N. A. N. A. Patented [7]
Aryl cyclopropylamine derivative 4 DM0C1ZO N. A. N. A. Patented [7]
Aryl cyclopropylamine derivative 5 DM6CK7J N. A. N. A. Patented [7]
Benzenamine derivative 1 DM6PMZC N. A. N. A. Patented [7]
Benzenamine derivative 2 DMDZ7QS N. A. N. A. Patented [7]
Benzenamine derivative 3 DM8UXZ3 N. A. N. A. Patented [7]
Benzenamine derivative 4 DMQT7HV N. A. N. A. Patented [7]
Cyclic peptide derivative 1 DM78NOU N. A. N. A. Patented [7]
Cyclopropylamine derivative 1 DMXN361 N. A. N. A. Patented [7]
Cyclopropylamine derivative 10 DMZ5WN8 N. A. N. A. Patented [7]
Cyclopropylamine derivative 11 DMMJ0YN N. A. N. A. Patented [7]
Cyclopropylamine derivative 12 DMV4I0K N. A. N. A. Patented [7]
Cyclopropylamine derivative 13 DMXNVD4 N. A. N. A. Patented [7]
Cyclopropylamine derivative 3 DM6E9L4 N. A. N. A. Patented [7]
Cyclopropylamine derivative 4 DMOCF4Y N. A. N. A. Patented [7]
Cyclopropylamine derivative 5 DM5BCGD N. A. N. A. Patented [7]
Cyclopropylamine derivative 6 DMB2RKC N. A. N. A. Patented [7]
Cyclopropylamine derivative 7 DM3X4PJ N. A. N. A. Patented [7]
Cyclopropylamine derivative 8 DMA89WQ N. A. N. A. Patented [7]
Cyclopropylamine derivative 9 DMX7YAL N. A. N. A. Patented [7]
Heteroaryl-cyclopropylamine derivative 1 DMRF58Q N. A. N. A. Patented [7]
Heteroaryl-cyclopropylamine derivative 2 DM9NE5T N. A. N. A. Patented [7]
Heteroaryl-cyclopropylamine derivative 3 DMH9EQ1 N. A. N. A. Patented [7]
Heteroaryl-cyclopropylamine derivative 4 DMMU01R N. A. N. A. Patented [7]
N-(2-phenylcyclopropyl) amino acid derivative 1 DMH7T8C N. A. N. A. Patented [7]
N-(2-phenylcyclopropyl) amino acid derivative 2 DM6YV3O N. A. N. A. Patented [7]
N-(2-phenylcyclopropyl) amino acid derivative 3 DMFBRSL N. A. N. A. Patented [7]
N6-cyclopropyllydine derivative 1 DMRHVWA N. A. N. A. Patented [7]
PMID25399762-Compound-Table 6-10 DM4UM03 N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-11 DMYGTU2 N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-12 DMZ07RP N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-13 DM6LR42 N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-14 DMZHB9Y N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-15 DMCHWSF N. A. N. A. Patented [8]
PMID25399762-Compound-Table 6-9 DMDWIPG N. A. N. A. Patented [8]
PMID27019002-Compound-13 DMD0HAT N. A. N. A. Patented [7]
PMID27019002-Compound-16 DMZ9T8H N. A. N. A. Patented [7]
PMID27019002-Compound-17 DM7JASU N. A. N. A. Patented [7]
PMID27019002-Compound-20a DMRX748 N. A. N. A. Patented [7]
PMID27019002-Compound-20b DMYRV8I N. A. N. A. Patented [7]
PMID27019002-Compound-21a DMC6AF2 N. A. N. A. Patented [7]
PMID27019002-Compound-21b DMMC31N N. A. N. A. Patented [7]
PMID27019002-Compound-21c DMWZOKP N. A. N. A. Patented [7]
PMID27019002-Compound-28 DM1R6GA N. A. N. A. Patented [7]
PMID27019002-Compound-28a DM954C8 N. A. N. A. Patented [7]
PMID27019002-Compound-31a DMRWGHN N. A. N. A. Patented [7]
PMID27019002-Compound-31b DMJ1K4Y N. A. N. A. Patented [7]
PMID27019002-Compound-37a DMMB6XC N. A. N. A. Patented [7]
PMID27019002-Compound-37b DMCIT5A N. A. N. A. Patented [7]
PMID27019002-Compound-41 DMVLXRB N. A. N. A. Patented [7]
PMID27019002-Compound-42a DM42VUQ N. A. N. A. Patented [7]
PMID27019002-Compound-42b DMHJBRO N. A. N. A. Patented [7]
PMID27019002-Compound-43a DMMOVGU N. A. N. A. Patented [7]
PMID27019002-Compound-43b DMIMFND N. A. N. A. Patented [7]
PMID27019002-Compound-43c DM72TBJ N. A. N. A. Patented [7]
PMID27019002-Compound-44 DM5HUCR N. A. N. A. Patented [7]
PMID27019002-Compound-45 DM3G6YV N. A. N. A. Patented [7]
PMID27019002-Compound-46 DMQPU7K N. A. N. A. Patented [7]
PMID27019002-Compound-47 DMRLWP9 N. A. N. A. Patented [7]
PMID27019002-Compound-48 DMIO8J3 N. A. N. A. Patented [7]
PMID27019002-Compound-49 DMP6WCX N. A. N. A. Patented [7]
PMID27019002-Compound-50 DM4D75L N. A. N. A. Patented [7]
PMID27019002-Compound-7 DMB0S52 N. A. N. A. Patented [7]
Pyrimidine derivative 16 DM3GYPD N. A. N. A. Patented [7]
Pyrimidine derivative 17 DM7YA9Z N. A. N. A. Patented [7]
Pyrimidine derivative 18 DMIZTKS N. A. N. A. Patented [7]
Tarnylcypromine derivative 1 DMQKOMR N. A. N. A. Patented [7]
Tarnylcypromine derivative 2 DMEJR2F N. A. N. A. Patented [7]
Tarnylcypromine derivative 3 DMKJOMC N. A. N. A. Patented [7]
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⏷ Show the Full List of 69 Patented Agent(s)
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
GSK-LSD1 DMHJU7A Discovery agent N.A. Investigative [9]
NCL-1 DMH1BVG Discovery agent N.A. Investigative [10]
OG-L002 DM0PMKW Discovery agent N.A. Investigative [11]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Lung cancer 2C82 Lung tissue 1.51E-76 0.51 1.91
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References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 Clinical pipeline report, company report or official report of Oryzon Genomics Boston, MA
3 Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis. Pharmaceutics. 2022 Jul 6;14(7):1420.
4 A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC. Cancer Cell. 2015 Jul 13;28(1):57-69.
5 Scaffolding LSD1 Inhibitors Impair NK Cell Metabolism and Cytotoxic Function Through Depletion of Glutathione. Front Immunol. 2020 Sep 17;11:2196.
6 Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
7 LSD1 inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2016 May;26(5):565-80.
8 Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
9 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2669).
10 Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor. Bioorg Med Chem. 2011 Jun 15;19(12):3702-8.
11 A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency. MBio. 2013 Feb 5;4(1):e00558-12.