histone deacetylase 8 | 3.5.1.- Histone deacetylases (HDACs) | IUPHAR/BPS Guide to PHARMACOLOGY

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histone deacetylase 8

Target not currently curated in GtoImmuPdb

Target id: 2619

Nomenclature: histone deacetylase 8

Family: 3.5.1.- Histone deacetylases (HDACs)

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
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction
EC Number:

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter 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]
marbostat-100 Hs Inhibition 6.8 pKi 13
pKi 6.8 (Ki 1.73x10-7 M) [13]
Description: In vitro biochemical assay using recombinant purified human HDAC8.
vorinostat Hs Inhibition 6.3 – 6.7 pKi 2,15
pKi 6.3 – 6.7 (Ki 4.8x10-7 – 2.05x10-7 M) [2,15]
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 12
pIC50 7.0 (IC50 1x10-7 M) [12]
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]
suprastat Hs Inhibition 6.3 pIC50 11
pIC50 6.3 (IC50 4.98x10-7 M) [11]
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]
SS-208 Hs Inhibition 5.9 pIC50 14
pIC50 5.9 (IC50 1.23x10-6 M) [14]
droxinostat Hs Inhibition 5.8 pIC50 16
pIC50 5.8 (IC50 1.46x10-6 M) [16]
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
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0031397 negative regulation of protein ubiquitination IDA
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.


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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. Transplantation, 100 (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 Lett, 2 (1): 39-42. [PMID:21874153]

6. Huang P, Almeciga-Pinto I, Jarpe M, van Duzer JH, Mazitschek R, Yang M, Jones SS, Quayle SN. (2017) Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. Oncotarget, 8 (2): 2694-2707. [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. Noonepalle S, Shen S, Ptáček J, Tavares MT, Zhang G, Stránský J, Pavlíček J, Ferreira GM, Hadley M, Pelaez G et al.. (2020) Rational Design of Suprastat: A Novel Selective Histone Deacetylase 6 Inhibitor with the Ability to Potentiate Immunotherapy in Melanoma Models. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00567 [PMID:32815366]

12. 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. Blood, 119 (11): 2579-89. [PMID:22262760]

13. Sellmer A, Stangl H, Beyer M, Grünstein E, Leonhardt M, Pongratz H, Eichhorn E, Elz S, Striegl B, Jenei-Lanzl Z et al.. (2018) Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors. J. Med. Chem., 61 (8): 3454-3477. [PMID:29589441]

14. Shen S, Hadley M, Ustinova K, Pavlicek J, Knox T, Noonepalle S, Tavares MT, Zimprich CA, Zhang G, Robers MB et al.. (2019) Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models. J. Med. Chem., 62 (18): 8557-8577. [PMID:31414801]

15. 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]

16. 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 07/09/2020. Accessed on 30/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2619.