lysine demethylase 6B | 1.14.11.- Histone demethylases | IUPHAR/BPS Guide to PHARMACOLOGY

lysine demethylase 6B

Target id: 2685

Nomenclature: lysine demethylase 6B

Family: 1.14.11.- Histone demethylases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     lysine demethylase 6B has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1682 17p13.1 KDM6B lysine demethylase 6B
Mouse - 1641 11 B3 Kdm6b KDM1 lysine (K)-specific demethylase 6B
Rat - 1361 10q24 Kdm6b lysine demethylase 6B
Previous and Unofficial Names
JMJD3 | KDM1 lysine (K)-specific demethylase 6B | lysine (K)-specific demethylase 6B
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GSK-J1 Hs Inhibition 7.2 – 7.6 pIC50 5-6
pIC50 7.2 – 7.6 (IC50 6x10-8 – 2.8x10-8 M) [5-6]
compound 3 [PMID: 29633584] Hs Inhibition 5.8 pIC50 4
pIC50 5.8 (IC50 1.52x10-6 M) [4]
IOX1 Hs Inhibition 5.8 pIC50 8
pIC50 5.8 (IC50 1.6x10-6 M) [8]
GSK-J4 Hs Inhibition 5.1 pIC50 5
pIC50 5.1 (IC50 8.6x10-6 M) [5]
Immunopharmacology Comments
In relation to the immune system, overexpression of JMJD3 is associated with inflammation [2-3] and with immune cell cancers such as T‐cell acute lymphoblastic leukemia and Hodgkin's lymphoma [1,7]. Selective JMJD3 inhibitors which restore H3K27 tri-methylation marks on KDM6B transcriptional target genes are being developed e.g. Compound 3 [PMID: 29633584], with clinical efficacy applicable to the treatment of cancer, inflammation and neurological disorders being the ultimate goal.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002437 inflammatory response to antigenic stimulus IEA

References

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1. Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M, Helin K, Christensen J, Rowe M, Murray PG et al.. (2011) The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma. Oncogene, 30 (17): 2037-43. [PMID:21242977]

2. De Santa F, Narang V, Yap ZH, Tusi BK, Burgold T, Austenaa L, Bucci G, Caganova M, Notarbartolo S, Casola S et al.. (2009) Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J., 28 (21): 3341-52. [PMID:19779457]

3. De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. (2007) The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell, 130 (6): 1083-94. [PMID:17825402]

4. Giordano A, Del Gaudio F, Johansson C, Riccio R, Oppermann U, Di Micco S. (2018) Virtual Fragment Screening Identification of a Quinoline-5,8-dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor. ChemMedChem, 13 (12): 1160-1164. [PMID:29633584]

5. 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]

6. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H et al.. (2012) A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature, 488 (7411): 404-8. [PMID:22842901]

7. Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L, Loizou E, Holmfeldt L, Strikoudis A, King B et al.. (2014) Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature, 514 (7523): 513-7. [PMID:25132549]

8. Schiller R, Scozzafava G, Tumber A, Wickens JR, Bush JT, Rai G, Lejeune C, Choi H, Yeh TL, Chan MC et al.. (2014) A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem, 9 (3): 566-71. [PMID:24504543]

How to cite this page

1.14.11.- Histone demethylases: lysine demethylase 6B. Last modified on 28/05/2018. Accessed on 21/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2685.