histone deacetylase 3

Target id: 2617

Nomenclature: histone deacetylase 3

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 :     histone deacetylase 3 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 428 5q31.1-q31.2 HDAC3 histone deacetylase 3
Mouse - 424 18 B3 Hdac3 histone deacetylase 3
Rat - 428 18p11 Hdac3 histone deacetylase 3
Previous and Unofficial Names
HD3 | RPD3
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
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 3
pKi 9.8 (Ki 1.5x10-10 M) [3]
apicidin Hs Inhibition 9.6 pKi 3
pKi 9.6 (Ki 2.6x10-10 M) [3]
trichostatin A Hs Inhibition 9.3 pKi 3
pKi 9.3 (Ki 5x10-10 M) [3]
belinostat Hs Inhibition 8.8 pKi 3
pKi 8.8 (Ki 1.5x10-9 M) [3]
givinostat Hs Inhibition 8.5 pKi 3
pKi 8.5 (Ki 3x10-9 M) [3]
scriptaid Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.1x10-9 M) [3]
dacinostat Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.2x10-9 M) [3]
vorinostat Hs Inhibition 8.3 pKi 3
pKi 8.3 (Ki 5x10-9 M) [3]
RGFP109 Hs Inhibition 8.3 pKi 16
pKi 8.3 (Ki 5x10-9 M) [16]
mocetinostat Hs Inhibition 6.6 pKi 3
pKi 6.6 (Ki 2.65x10-7 M) [3]
entinostat Hs Inhibition 6.4 pKi 3
pKi 6.4 (Ki 3.6x10-7 M) [3]
tacedinaline Hs Inhibition 6.3 pKi 3
pKi 6.3 (Ki 5.5x10-7 M) [3]
panobinostat Hs Inhibition 8.4 pEC50 9
pEC50 8.4 (EC50 4x10-9 M) [9]
givinostat Hs Inhibition 7.7 pEC50 9
pEC50 7.7 (EC50 2.1x10-8 M) [9]
belinostat Hs Inhibition 7.5 pEC50 9
pEC50 7.5 (EC50 3x10-8 M) [9]
apicidin Hs Inhibition 7.4 – 7.5 pEC50 9
pEC50 7.5 (EC50 3x10-8 M) [9]
pEC50 7.4 (EC50 4.3x10-8 M) [9]
entinostat Hs Inhibition 5.6 pEC50 9
pEC50 5.6 (EC50 2.311x10-6 M) [9]
CUDC-907 Hs Inhibition 8.7 pIC50 15
pIC50 8.7 (IC50 1.8x10-9 M) [15]
BML-281 Hs Inhibition >8.7 pIC50 10
pIC50 >8.7 (IC50 <2x10-9 M) [10]
quisinostat Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 4.86x10-9 M) [2]
CHR-3996 Hs Inhibition 8.1 pIC50 13
pIC50 8.1 (IC50 7x10-9 M) [13]
abexinostat Hs Inhibition 8.1 pIC50 4
pIC50 8.1 (IC50 8.2x10-9 M) [4]
CUDC-101 Hs Inhibition 8.0 pIC50 5
pIC50 8.0 (IC50 9.1x10-9 M) [5]
pracinostat Hs Inhibition 7.4 pIC50 14
pIC50 7.4 (IC50 4.3x10-8 M) [14]
citarinostat Hs Inhibition 7.3 pIC50 8
pIC50 7.3 (IC50 4.6x10-8 M) [8]
resminostat Hs Inhibition 7.3 pIC50 12
pIC50 7.3 (IC50 5.01x10-8 M) [12]
ricolinostat Hs Inhibition 7.3 pIC50 17
pIC50 7.3 (IC50 5.1x10-8 M) [17]
RGFP966 Hs Inhibition 7.1 pIC50 11
pIC50 7.1 (IC50 8x10-8 M) [11]
KA1010 Hs Inhibition 6.2 pIC50 6
pIC50 6.2 (IC50 7.1x10-7 M) [6]
butyric acid Hs Inhibition 5.1 pIC50 7
pIC50 5.1 (IC50 9x10-6 M) [7]
droxinostat Hs Inhibition 4.8 pIC50 18
pIC50 4.8 (IC50 1.69x10-5 M) [18]
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].
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. Transplantation100 (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 Lett2 (1): 39-42. [PMID:21874153]

8. 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]

9. 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]

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. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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 ONE5 (1): e8825. [PMID:20098685]

17. 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]

18. 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 25/09/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2617.