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histone deacetylase 2

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Target not currently curated in GtoImmuPdb

Target id: 2616

Nomenclature: histone deacetylase 2

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 - 488 6q21 HDAC2 histone deacetylase 2
Mouse - 488 10 B1 Hdac2 histone deacetylase 2
Rat - - 20q12 Hdac2 histone deacetylase 2
Previous and Unofficial Names Click here for help
RPD3 | YAF1
Database Links Click here for help
Alphafold Q92769 (Hs), P70288 (Mm)
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 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 10.4 pKi 2
⤷ pKi 10.4 (Ki 3.8x10-11 M) [2]
apicidin Small molecule or natural product Click here for species-specific activity table Guide to Malaria Pharmacology Ligand Hs Inhibition 9.9 pKi 2
⤷ pKi 9.9 (Ki 1.2x10-10 M) [2]
trichostatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.2 pKi 2
⤷ pKi 9.2 (Ki 6.5x10-10 M) [2]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pKi 2
⤷ pKi 9.1 (Ki 8.5x10-10 M) [2]
dacinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pKi 2
⤷ pKi 8.9 (Ki 1.4x10-9 M) [2]
vorinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pKi 2
⤷ pKi 8.8 (Ki 1.6x10-9 M) [2]
scriptaid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pKi 2
⤷ pKi 8.7 (Ki 2.2x10-9 M) [2]
givinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 2
⤷ pKi 8.5 (Ki 3x10-9 M) [2]
mocetinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pKi 2
⤷ pKi 7.5 (Ki 3.4x10-8 M) [2]
entinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pKi 2
⤷ pKi 7.2 (Ki 6.5x10-8 M) [2]
tacedinaline Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pKi 2
⤷ pKi 6.8 (Ki 1.5x10-7 M) [2]
marbostat-100 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pKi 16
⤷ pKi 6.1 (Ki 7.74x10-7 M) [16]
Description: In vitro biochemical assay using recombinant purified human HDAC2.
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 8.5 pEC50 9
⤷ pEC50 8.5 (EC50 3x10-9 M) [9]
givinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pEC50 9
⤷ pEC50 7.3 (EC50 5.6x10-8 M) [9]
apicidin Small molecule or natural product Click here for species-specific activity table Guide to Malaria Pharmacology Ligand Hs Inhibition 6.9 pEC50 9
⤷ pEC50 6.9 (EC50 1.2x10-7 M) [9]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pEC50 9
⤷ pEC50 6.9 (EC50 1.25x10-7 M) [9]
entinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pEC50 9
⤷ pEC50 5.9 (EC50 1.155x10-6 M) [9]
santacruzamate A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.9 pIC50 13
⤷ pIC50 9.9 (IC50 1.19x10-10 M) [13]
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 9.5 pIC50 1
⤷ pIC50 9.5 (IC50 3.3x10-10 M) [1]
martinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 17
⤷ pIC50 8.7 (IC50 2x10-9 M) [17]
CHR-3996 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 11
⤷ pIC50 8.4 (IC50 4x10-9 M) [11]
fimepinostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 14
⤷ pIC50 8.3 (IC50 5x10-9 M) [14]
CUDC-101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 3
⤷ pIC50 7.9 (IC50 1.26x10-8 M) [3]
citarinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 7
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [7]
ricolinostat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 15
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [15]
ACY-738 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 8
⤷ pIC50 6.9 (IC50 1.28x10-7 M) [8]
suprastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 12
⤷ pIC50 6.8 (IC50 1.76x10-7 M) [12]
BML-281 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 10
⤷ pIC50 6.6 (IC50 2.38x10-7 M) [10]
KA1010 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.8 pIC50 4
⤷ pIC50 5.8 (IC50 1.542x10-6 M) [4]
butyric acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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
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, 583 (7816): 459-468. [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. 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]

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. 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]

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. 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]

14. 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]

15. 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]

16. 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]

17. 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]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): histone deacetylase 2. Last modified on 07/09/2020. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2616.