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histone deacetylase 3

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2617

Nomenclature: histone deacetylase 3

Family: 3.5.1.- Histone deacetylases (HDACs)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 428 5q31.3 HDAC3 histone deacetylase 3
Mouse - 424 18 B3 Hdac3 histone deacetylase 3
Rat - 428 18p11 Hdac3 histone deacetylase 3
Previous and Unofficial Names Click here for help
HD3 | RPD3
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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]
apicidin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.6 pKi 3
pKi 9.6 (Ki 2.6x10-10 M) [3]
trichostatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pKi 3
pKi 9.3 (Ki 5x10-10 M) [3]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pKi 3
pKi 8.8 (Ki 1.5x10-9 M) [3]
givinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 3
pKi 8.5 (Ki 3x10-9 M) [3]
scriptaid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.1x10-9 M) [3]
dacinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.2x10-9 M) [3]
vorinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pKi 3
pKi 8.3 (Ki 5x10-9 M) [3]
RGFP109 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pKi 18
pKi 8.3 (Ki 5x10-9 M) [18]
mocetinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pKi 3
pKi 6.6 (Ki 2.65x10-7 M) [3]
entinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pKi 3
pKi 6.4 (Ki 3.6x10-7 M) [3]
tacedinaline Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pKi 3
pKi 6.3 (Ki 5.5x10-7 M) [3]
panobinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pEC50 10
pEC50 8.4 (EC50 4x10-9 M) [10]
givinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pEC50 10
pEC50 7.7 (EC50 2.1x10-8 M) [10]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pEC50 10
pEC50 7.5 (EC50 3x10-8 M) [10]
apicidin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 – 7.5 pEC50 10
pEC50 7.5 (EC50 3x10-8 M) [10]
pEC50 7.4 (EC50 4.3x10-8 M) [10]
entinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.6 pEC50 10
pEC50 5.6 (EC50 2.311x10-6 M) [10]
martinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.2 pIC50 20
pIC50 9.2 (IC50 6x10-10 M) [20]
fimepinostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 17
pIC50 8.7 (IC50 1.8x10-9 M) [17]
BML-281 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >8.7 pIC50 11
pIC50 >8.7 (IC50 <2x10-9 M) [11]
quisinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 4.86x10-9 M) [2]
CHR-3996 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 14
pIC50 8.1 (IC50 7x10-9 M) [14]
abexinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 4
pIC50 8.1 (IC50 8.2x10-9 M) [4]
CUDC-101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 5
pIC50 8.0 (IC50 9.1x10-9 M) [5]
pracinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 16
pIC50 7.4 (IC50 4.3x10-8 M) [16]
citarinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 8
pIC50 7.3 (IC50 4.6x10-8 M) [8]
resminostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 13
pIC50 7.3 (IC50 5.01x10-8 M) [13]
ricolinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 19
pIC50 7.3 (IC50 5.1x10-8 M) [19]
RGFP966 Small molecule or natural product Hs Inhibition 7.1 pIC50 12
pIC50 7.1 (IC50 8x10-8 M) [12]
ACY-738 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 9
pIC50 6.7 (IC50 2.18x10-7 M) [9]
suprastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 15
pIC50 6.4 (IC50 3.52x10-7 M) [15]
KA1010 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.2 pIC50 6
pIC50 6.2 (IC50 7.1x10-7 M) [6]
butyric acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.1 pIC50 7
pIC50 5.1 (IC50 9x10-6 M) [7]
droxinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.8 pIC50 21
pIC50 4.8 (IC50 1.69x10-5 M) [21]
Inhibitor Comments
Vorinostat has high affinity for HDACs 2, 3, 6, 9, 10 and 11, but 10-fold lower affinity for HDAC8
Immunopharmacology Comments
A 2017 study reports that HDAC3 (more so than HDACs -6, -1/2, or -8) regulates inflammatory gene expression in rheumatoid arthritis fibroblast-like synoviocytes, and is required for type I IFN production [1].
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0031398 positive regulation of protein ubiquitination ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0032692 negative regulation of interleukin-1 production ISO
GO:0032720 negative regulation of tumor necrosis factor production ISO
General Comments
HDAC3 is a Class I histone deacetylase.

References

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1. Angiolilli C, Kabala PA, Grabiec AM, Van Baarsen IM, Ferguson BS, García S, Malvar Fernandez B, McKinsey TA, Tak PP, Fossati G et al.. (2017) Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes. Ann. Rheum. Dis., 76 (1): 277-285. [PMID:27457515]

2. 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]

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. Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. (2006) CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol. Cancer Ther., 5 (5): 1309-17. [PMID:16731764]

5. 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]

6. 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]

7. 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]

8. 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]

9. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O. (2014) Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology, 39 (2): 389-400. [PMID:23954848]

10. 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]

11. 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]

12. Malvaez M, McQuown SC, Rogge GA, Astarabadi M, Jacques V, Carreiro S, Rusche JR, Wood MA. (2013) HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc. Natl. Acad. Sci. U.S.A., 110 (7): 2647-52. [PMID:23297220]

13. 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]

14. Moffat D, Patel S, Day F, Belfield A, Donald A, Rowlands M, Wibawa J, Brotherton D, Stimson L, Clark V et al.. (2010) Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I selective orally active histone deacetylase inhibitor. J. Med. Chem., 53 (24): 8663-78. [PMID:21080647]

15. 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]

16. Novotny-Diermayr V, Sangthongpitag K, Hu CY, Wu X, Sausgruber N, Yeo P, Greicius G, Pettersson S, Liang AL, Loh YK et al.. (2010) SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol. Cancer Ther., 9 (3): 642-52. [PMID:20197387]

17. Qian C, Lai CJ, Bao R, Wang DG, Wang J, Xu GX, Atoyan R, Qu H, Yin L, Samson M et al.. (2012) Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin. Cancer Res., 18 (15): 4104-13. [PMID:22693356]

18. Rai M, Soragni E, Chou CJ, Barnes G, Jones S, Rusche JR, Gottesfeld JM, Pandolfo M. (2010) Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model. PLoS ONE, 5 (1): e8825. [PMID:20098685]

19. 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]

20. Wang C, Schroeder FA, Wey HY, Borra R, Wagner FF, Reis S, Kim SW, Holson EB, Haggarty SJ, Hooker JM. (2014) In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs. J. Med. Chem., 57 (19): 7999-8009. [PMID:25203558]

21. 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 3. Last modified on 07/09/2020. Accessed on 23/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2617.