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histone deacetylase 8

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Target not currently curated in GtoImmuPdb

Target id: 2619

Nomenclature: histone deacetylase 8

Family: 3.5.1.- Histone deacetylases (HDACs)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 377 Xq13.1 HDAC8 histone deacetylase 8
Mouse - 377 X D Hdac8 histone deacetylase 8
Rat - 377 Xq22 Hdac8 histone deacetylase 8
Previous and Unofficial Names Click here for help
RPD3
Database Links Click here for help
Alphafold Q9BY41 (Hs), Q8VH37 (Mm), B1WC68 (Rn)
BRENDA 3.5.1.98
CATH/Gene3D 3.40.800.20
ChEMBL Target CHEMBL3192 (Hs), CHEMBL2347 (Mm)
Ensembl Gene ENSG00000147099 (Hs), ENSMUSG00000067567 (Mm), ENSRNOG00000003122 (Rn)
Entrez Gene 55869 (Hs), 70315 (Mm), 363481 (Rn)
Human Protein Atlas ENSG00000147099 (Hs)
KEGG Enzyme 3.5.1.98
KEGG Gene hsa:55869 (Hs), mmu:70315 (Mm), rno:363481 (Rn)
OMIM 300269 (Hs)
Orphanet ORPHA290272 (Hs)
Pharos Q9BY41 (Hs)
RefSeq Nucleotide NM_018486 (Hs), NM_027382 (Mm), NM_001126373 (Rn)
RefSeq Protein NP_060956 (Hs), NP_081658 (Mm), NP_001119845 (Rn)
SynPHARM 79163 (in complex with trichostatin A)
78890 (in complex with vorinostat)
UniProtKB Q9BY41 (Hs), Q8VH37 (Mm), B1WC68 (Rn)
Wikipedia HDAC8 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.5.1.98

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
romidepsin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 9.8 pKi 3
⤷ pKi 9.8 (Ki 1.5x10-10 M) [3]
trichostatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pKi 3
⤷ pKi 8.4 (Ki 4.5x10-9 M) [3]
SZUH280 Small molecule or natural product Hs Inhibition ~8.0 pKi 2
⤷ pKi ~8.0 (Ki ~1x10-8 M) [2]
Description: Inhibition constant for the parent HDAC8 inhibitor PCI-34051
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pKi 3
⤷ pKi 7.6 (Ki 2.5x10-8 M) [3]
givinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 3
⤷ pKi 7.4 (Ki 3.9x10-8 M) [3]
apicidin Small molecule or natural product Click here for species-specific activity table Guide to Malaria Pharmacology Ligand Hs Inhibition 7.3 pKi 3
⤷ pKi 7.3 (Ki 4.9x10-8 M) [3]
scriptaid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pKi 3
⤷ pKi 7.0 (Ki 1.05x10-7 M) [3]
marbostat-100 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pKi 14
⤷ pKi 6.8 (Ki 1.73x10-7 M) [14]
Description: In vitro biochemical assay using recombinant purified human HDAC8.
vorinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 – 6.7 pKi 3,16
⤷ pKi 6.3 – 6.7 (Ki 4.8x10-7 – 2.05x10-7 M) [3,16]
dacinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pKi 3
⤷ pKi 6.5 (Ki 3.4x10-7 M) [3]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pEC50 8
⤷ pEC50 6.7 (EC50 2.16x10-7 M) [8]
panobinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs Inhibition 6.6 pEC50 8
⤷ pEC50 6.6 (EC50 2.48x10-7 M) [8]
apicidin Small molecule or natural product Click here for species-specific activity table Guide to Malaria Pharmacology Ligand Hs Inhibition 6.2 pEC50 8
⤷ pEC50 6.2 (EC50 5.75x10-7 M) [8]
compound 25ap [PMID: 37796543] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.8 pIC50 19
⤷ pIC50 9.8 (IC50 1.6x10-10 M) [19]
quisinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs Inhibition 8.4 pIC50 1
⤷ pIC50 8.4 (IC50 4.26x10-9 M) [1]
CUDC-101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 4
⤷ pIC50 7.1 (IC50 7.98x10-8 M) [4]
ricolinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 13
⤷ pIC50 7.0 (IC50 1x10-7 M) [13]
citarinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pIC50 7
⤷ pIC50 6.9 (IC50 1.37x10-7 M) [7]
J27644 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 18
⤷ pIC50 6.8 (IC50 1.51x10-7 M) [18]
KA1010 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 5
⤷ pIC50 6.4 (IC50 3.63x10-7 M) [5]
suprastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 12
⤷ pIC50 6.3 (IC50 4.98x10-7 M) [12]
tubastatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 9
⤷ pIC50 6.1 (IC50 8.14x10-7 M) [9]
resminostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pIC50 11
⤷ pIC50 6.1 (IC50 8.77x10-7 M) [11]
SS-208 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 15
⤷ pIC50 5.9 (IC50 1.23x10-6 M) [15]
droxinostat Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 pIC50 17
⤷ pIC50 5.8 (IC50 1.46x10-6 M) [17]
BML-281 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.1 pIC50 10
⤷ pIC50 5.1 (IC50 8.104x10-6 M) [10]
butyric acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.8 pIC50 6
⤷ pIC50 4.8 (IC50 1.5x10-5 M) [6]
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
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ. (2008) A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia, 22 (5): 1026-34. [PMID:18256683]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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.

10. 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]

11. 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]

12. 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, 63 (18): 10246-10262. [PMID:32815366]

13. 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]

14. 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]

15. 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]

16. 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]

17. 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]

18. Yu WC, Yeh TY, Ye CH, Chong PCT, Ho YH, So DK, Yap KY, Peng GR, Shao CH, Jagtap AD et al.. (2023) Discovery of HDAC6, HDAC8, and 6/8 Inhibitors and Development of Cell-Based Drug Screening Models for the Treatment of TGF-β-Induced Idiopathic Pulmonary Fibrosis. J Med Chem, 66 (15): 10528-10557. [PMID:37463500]

19. Zhao C, Zhang Y, Zhang J, Li S, Liu M, Geng Y, Liu F, Chai Q, Meng H, Li M et al.. (2023) Discovery of Novel Fedratinib-Based HDAC/JAK/BRD4 Triple Inhibitors with Remarkable Antitumor Activity against Triple Negative Breast Cancer. J Med Chem, 66 (20): 14150-14174. [PMID:37796543]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): histone deacetylase 8. Last modified on 06/10/2023. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2619.