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lysine demethylase 6A

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2684

Nomenclature: lysine demethylase 6A

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 - 1401 Xp11.3 KDM6A lysine demethylase 6A
Mouse - 1401 X 13.45 cM Kdm6a lysine (K)-specific demethylase 6A
Rat - - X Uty ubiquitously transcribed tetratricopeptide repeat containing, Y-linked
Previous and Unofficial Names Click here for help
UTX | lysine (K)-specific demethylase 6A | Kdm6a | ubiquitously transcribed tetratricopeptide repeat containing, Y-linked | ubiquitously transcribed tetratricopeptide repeat gene, Y chromosome | ubiquitously transcribed tetratricopeptide repeat gene | ubiquitously transcribed tetratricopeptide repeat containing
Database Links Click here for help
Alphafold
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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK-J1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 2
pIC50 7.3 (IC50 5.3x10-8 M) [2]
GSK-J4 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.2 pIC50 2
pIC50 5.2 (IC50 6.6x10-6 M) [2]
KDM5 inhibitor N71 Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.2 pIC50 3
pIC50 <4.2 (IC50 >6x10-5 M) [3]
Immunopharmacology Comments
KDM6A and KDM6B have been reported as key regulators of metabolic switches that are involved in metabolic reprogramming of human T helper cell subsets [1]. In vitro, inhibition by GSK-J4 (the ester prodrug of GSK-J1, a KDM6A/B inhibitor) increases repressive H3K27me3 histone marks which causes down-regulation of the key transcription factor RORγt during Th17 differentiation, and in mature Th17 cells leads to metabolic reprogramming, suppression of IL-17 cytokine levels and reduced proliferation. This work suggests that inhibiting KDM6 demethylases may be an effective intervention in autoimmune inflammation.

References

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1. Cribbs AP, Terlecki-Zaniewicz S, Philpott M, Baardman J, Ahern D, Lindow M, Obad S, Oerum H, Sampey B, Mander PK et al.. (2020) Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism. Proc Natl Acad Sci USA, 117 (11): 6056-6066. [PMID:32123118]

2. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M, Gerlach LO, Birk P, Helin K. (2014) Inhibition of demethylases by GSK-J1/J4. Nature, 514 (7520): E1-2. [PMID:25279926]

3. Horton JR, Woodcock CB, Chen Q, Liu X, Zhang X, Shanks J, Rai G, Mott BT, Jansen DJ, Kales SC et al.. (2018) Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A. J Med Chem, 61 (23): 10588-10601. [PMID:30392349]

How to cite this page

1.14.11.- Histone demethylases: lysine demethylase 6A. Last modified on 04/03/2020. Accessed on 06/12/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2684.