histone deacetylase 2 | 3.5.1.- Histone deacetylases (HDACs) | IUPHAR/BPS Guide to PHARMACOLOGY

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histone deacetylase 2

Target not currently curated in GtoImmuPdb

Target id: 2616

Nomenclature: histone deacetylase 2

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

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 488 6q21 HDAC2 histone deacetylase 2
Mouse - 488 10 B1 Hdac2 histone deacetylase 2
Rat - - 20q12 Hdac2 histone deacetylase 2
Previous and Unofficial Names
RPD3 | YAF1
Database Links
BRENDA 3.5.1.98
CATH/Gene3D 3.40.800.20
ChEMBL Target CHEMBL1937 (Hs)
DrugBank Target Q92769 (Hs)
Ensembl Gene ENSG00000196591 (Hs), ENSMUSG00000019777 (Mm), ENSRNOG00000000604 (Rn)
Entrez Gene 3066 (Hs), 15182 (Mm), 84577 (Rn)
Human Protein Atlas ENSG00000196591 (Hs)
KEGG Enzyme 3.5.1.98
KEGG Gene hsa:3066 (Hs), mmu:15182 (Mm), rno:84577 (Rn)
OMIM 605164 (Hs)
Pharos Q92769 (Hs)
RefSeq Nucleotide NM_001527 (Hs), NM_008229 (Mm), NM_053447 (Rn)
RefSeq Protein NP_001518 (Hs), NP_032255 (Mm), NP_445899 (Rn)
SynPHARM 78885 (in complex with vorinostat)
UniProtKB Q92769 (Hs), P70288 (Mm)
Wikipedia HDAC2 (Hs)
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 Value Parameter Reference
romidepsin Hs Inhibition 10.4 pKi 2
⤷ pKi 10.4 (Ki 3.8x10-11 M) [2]
apicidin Hs Inhibition 9.9 pKi 2
⤷ pKi 9.9 (Ki 1.2x10-10 M) [2]
trichostatin A Hs Inhibition 9.2 pKi 2
⤷ pKi 9.2 (Ki 6.5x10-10 M) [2]
belinostat Hs Inhibition 9.1 pKi 2
⤷ pKi 9.1 (Ki 8.5x10-10 M) [2]
dacinostat Hs Inhibition 8.9 pKi 2
⤷ pKi 8.9 (Ki 1.4x10-9 M) [2]
vorinostat Hs Inhibition 8.8 pKi 2
⤷ pKi 8.8 (Ki 1.6x10-9 M) [2]
scriptaid Hs Inhibition 8.7 pKi 2
⤷ pKi 8.7 (Ki 2.2x10-9 M) [2]
givinostat Hs Inhibition 8.5 pKi 2
⤷ pKi 8.5 (Ki 3x10-9 M) [2]
mocetinostat Hs Inhibition 7.5 pKi 2
⤷ pKi 7.5 (Ki 3.4x10-8 M) [2]
entinostat Hs Inhibition 7.2 pKi 2
⤷ pKi 7.2 (Ki 6.5x10-8 M) [2]
tacedinaline Hs Inhibition 6.8 pKi 2
⤷ pKi 6.8 (Ki 1.5x10-7 M) [2]
marbostat-100 Hs Inhibition 6.1 pKi 14
⤷ pKi 6.1 (Ki 7.74x10-7 M) [14]
Description: In vitro biochemical assay using recombinant purified human HDAC2.
panobinostat Hs Inhibition 8.5 pEC50 8
⤷ pEC50 8.5 (EC50 3x10-9 M) [8]
givinostat Hs Inhibition 7.3 pEC50 8
⤷ pEC50 7.3 (EC50 5.6x10-8 M) [8]
apicidin Hs Inhibition 6.9 pEC50 8
⤷ pEC50 6.9 (EC50 1.2x10-7 M) [8]
belinostat Hs Inhibition 6.9 pEC50 8
⤷ pEC50 6.9 (EC50 1.25x10-7 M) [8]
entinostat Hs Inhibition 5.9 pEC50 8
⤷ pEC50 5.9 (EC50 1.155x10-6 M) [8]
santacruzamate A Hs Inhibition 9.9 pIC50 11
⤷ pIC50 9.9 (IC50 1.19x10-10 M) [11]
quisinostat Hs Inhibition 9.5 pIC50 1
⤷ pIC50 9.5 (IC50 3.3x10-10 M) [1]
CHR-3996 Hs Inhibition 8.4 pIC50 10
⤷ pIC50 8.4 (IC50 4x10-9 M) [10]
fimepinostat Hs Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5x10-9 M) [12]
CUDC-101 Hs Inhibition 7.9 pIC50 3
⤷ pIC50 7.9 (IC50 1.26x10-8 M) [3]
citarinostat Hs Inhibition 7.3 pIC50 7
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [7]
ricolinostat Hs Inhibition 7.3 pIC50 13
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [13]
BML-281 Hs Inhibition 6.6 pIC50 9
⤷ pIC50 6.6 (IC50 2.38x10-7 M) [9]
KA1010 Hs Inhibition 5.8 pIC50 4
⤷ pIC50 5.8 (IC50 1.542x10-6 M) [4]
butyric acid Hs Inhibition 4.9 pIC50 5
⤷ pIC50 4.9 (IC50 1.2x10-5 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:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0032732 positive regulation of interleukin-1 production IEA
GO:0032760 positive regulation of tumor necrosis factor production IEA
General Comments
HDAC2 is a Class I histone deacetylase.

SARS-CoV-2/COVID-19
Experimental in vitro evidence, using affinity-purification mass spectrometry (AP-MS), indicates a protein-protein interaction between HDAC2 and the SARS-CoV-2 non-structural protein 5 (Nsp5) [6], although whether this interaction is realistic based on spatial distribution of the host and viral proteins within cells was not addressed in this study. Speculatively, HDAC2 ligands such as apicidin or valproic acid could be utilised to examine the effect of inhibiting the HDAC2/Nsp5 protein-protein interaction on SARS-CoV-2 pathobiology.

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. 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. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, [Epub ahead of print]. [PMID:32353859]

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 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. 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]

11. Pavlik CM, Wong CY, Ononye S, Lopez DD, Engene N, McPhail KL, Gerwick WH, Balunas MJ. (2013) Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp. J. Nat. Prod., 76 (11): 2026-33. [PMID:24164245]

12. 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]

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]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): histone deacetylase 2. Last modified on 27/03/2020. Accessed on 11/07/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2616.