histone deacetylase 8

Target id: 2619

Nomenclature: histone deacetylase 8

Family: 3.5.1.- Histone deacetylases (HDACs)

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 :     Currently no data for histone deacetylase 8 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 377 Xq13 HDAC8 histone deacetylase 8
Mouse - 377 X C3 Hdac8 histone deacetylase 8
Rat - 377 Xq31 Hdac8 histone deacetylase 8
Previous and Unofficial Names
RPD3
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.5.1.98

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
romidepsin Hs Inhibition 9.8 pKi 2
pKi 9.8 (Ki 1.5x10-10 M) [2]
trichostatin A Hs Inhibition 8.4 pKi 2
pKi 8.4 (Ki 4.5x10-9 M) [2]
belinostat Hs Inhibition 7.6 pKi 2
pKi 7.6 (Ki 2.5x10-8 M) [2]
givinostat Hs Inhibition 7.4 pKi 2
pKi 7.4 (Ki 3.9x10-8 M) [2]
apicidin Hs Inhibition 7.3 pKi 2
pKi 7.3 (Ki 4.9x10-8 M) [2]
scriptaid Hs Inhibition 7.0 pKi 2
pKi 7.0 (Ki 1.05x10-7 M) [2]
vorinostat Hs Inhibition 6.3 – 6.7 pKi 2,12
pKi 6.3 – 6.7 (Ki 4.8x10-7 – 2.05x10-7 M) [2,12]
dacinostat Hs Inhibition 6.5 pKi 2
pKi 6.5 (Ki 3.4x10-7 M) [2]
belinostat Hs Inhibition 6.7 pEC50 7
pEC50 6.7 (EC50 2.16x10-7 M) [7]
panobinostat Hs Inhibition 6.6 pEC50 7
pEC50 6.6 (EC50 2.48x10-7 M) [7]
apicidin Hs Inhibition 6.2 pEC50 7
pEC50 6.2 (EC50 5.75x10-7 M) [7]
quisinostat Hs Inhibition 8.4 pIC50 1
pIC50 8.4 (IC50 4.26x10-9 M) [1]
CUDC-101 Hs Inhibition 7.1 pIC50 3
pIC50 7.1 (IC50 7.98x10-8 M) [3]
ricolinostat Hs Inhibition 7.0 pIC50 11
pIC50 7.0 (IC50 1x10-7 M) [11]
citarinostat Hs Inhibition 6.9 pIC50 6
pIC50 6.9 (IC50 1.37x10-7 M) [6]
KA1010 Hs Inhibition 6.4 pIC50 4
pIC50 6.4 (IC50 3.63x10-7 M) [4]
tubastatin A Hs Inhibition 6.1 pIC50 8
pIC50 6.1 (IC50 8.14x10-7 M) [8]
resminostat Hs Inhibition 6.1 pIC50 10
pIC50 6.1 (IC50 8.77x10-7 M) [10]
droxinostat Hs Inhibition 5.8 pIC50 13
pIC50 5.8 (IC50 1.46x10-6 M) [13]
BML-281 Hs Inhibition 5.1 pIC50 9
pIC50 5.1 (IC50 8.104x10-6 M) [9]
butyric acid Hs Inhibition 4.8 pIC50 5
pIC50 4.8 (IC50 1.5x10-5 M) [5]
Inhibitor Comments
Vorinostat has high affinity for HDACs 2, 3, 6, 9, 10 and 11, but 10-fold lower affinity for HDAC8
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cornelia de Lange syndrome 5
Synonyms: Cornelia de Lange syndrome [Orphanet: ORPHA199] [Disease Ontology: DOID:11725]
Disease Ontology: DOID:11725
OMIM: 300882
Orphanet: ORPHA199
Disease:  Wilson-Turner X-linked mental retardation syndrome
Synonyms: Wilson-Turner syndrome [Orphanet: ORPHA3459]
OMIM: 309585
Orphanet: ORPHA3459
General Comments
HDAC8 is a Class I histone deacetylase.

References

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1. Arts J, King P, Mariën A, Floren W, Beliën A, Janssen L, Pilatte I, Roux B, Decrane L, Gilissen R et al.. (2009) JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin. Cancer Res.15 (22): 6841-51. [PMID:19861438]

2. Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R. (2010) Chemical phylogenetics of histone deacetylases. Nat. Chem. Biol.6 (3): 238-243. [PMID:20139990]

3. Cai X, Zhai HX, Wang J, Forrester J, Qu H, Yin L, Lai CJ, Bao R, Qian C. (2010) Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J. Med. Chem.53 (5): 2000-9. [PMID:20143778]

4. Ellis JD, Neil DA, Inston NG, Jenkinson E, Drayson MT, Hampson P, Shuttleworth SJ, Ready AR, Cobbold M. (2016) Inhibition of Histone Deacetylase 6 Reveals a Potent Immunosuppressant Effect in Models of Transplantation. Transplantation100 (8): 1667-74. [PMID:27222932]

5. Fass DM, Shah R, Ghosh B, Hennig K, Norton S, Zhao WN, Reis SA, Klein PS, Mazitschek R, Maglathlin RL et al.. (2010) Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin. ACS Med Chem Lett2 (1): 39-42. [PMID:21874153]

6. Huang P, Almeciga-Pinto I, Jarpe M, van Duzer JH, Mazitschek R, Yang M, Jones SS, Quayle SN. (2016) Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. Oncotarget,  [Epub ahead of print]. [PMID:27926524]

7. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N et al.. (2008) Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem. J.409 (2): 581-9. [PMID:17868033]

8. Kozikowski A, Butler KV, Kalin JH. (2014) HDAC inhibitors and therapeutic methods of using same. Patent number: US8748451. Assignee: The Board Of Trustees Of The University Of Illinois. Priority date: 22/07/2009. Publication date: 10/06/2014.

9. Kozikowski AP, Tapadar S, Luchini DN, Kim KH, Billadeau DD. (2008) Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J. Med. Chem.51 (15): 4370-3. [PMID:18642892]

10. Mandl-Weber S, Meinel FG, Jankowsky R, Oduncu F, Schmidmaier R, Baumann P. (2010) The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells. Br. J. Haematol.149 (4): 518-28. [PMID:20201941]

11. Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC et al.. (2012) Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood119 (11): 2579-89. [PMID:22262760]

12. Wang H, Lim ZY, Zhou Y, Ng M, Lu T, Lee K, Sangthongpitag K, Goh KC, Wang X, Wu X et al.. (2010) Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity. Bioorg. Med. Chem. Lett.20 (11): 3314-21. [PMID:20451378]

13. Wood TE, Dalili S, Simpson CD, Sukhai MA, Hurren R, Anyiwe K, Mao X, Suarez Saiz F, Gronda M, Eberhard Y et al.. (2010) Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol. Cancer Ther.9 (1): 246-56. [PMID:20053768]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): histone deacetylase 8. Last modified on 14/11/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2619.