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histone deacetylase 4

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Target id: 2659

Nomenclature: histone deacetylase 4

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 - 1084 2q37.3 HDAC4 histone deacetylase 4 5
Mouse - 1076 1 D Hdac4 histone deacetylase 4
Rat - 1077 9q36 Hdac4 histone deacetylase 4
Database Links Click here for help
Alphafold P56524 (Hs), Q6NZM9 (Mm)
BRENDA 3.5.1.98
CATH/Gene3D 3.40.800.20
ChEMBL Target CHEMBL3524 (Hs)
Ensembl Gene ENSG00000068024 (Hs), ENSMUSG00000026313 (Mm), ENSRNOG00000020372 (Rn)
Entrez Gene 9759 (Hs), 208727 (Mm), 363287 (Rn)
Human Protein Atlas ENSG00000068024 (Hs)
KEGG Enzyme 3.5.1.98
KEGG Gene hsa:9759 (Hs), mmu:208727 (Mm), rno:363287 (Rn)
OMIM 605314 (Hs)
Pharos P56524 (Hs)
RefSeq Nucleotide NM_006037 (Hs), NM_207225 (Mm), NM_053449 (Rn)
RefSeq Protein NP_006028 (Hs), NP_997108 (Mm), NP_445901 (Rn)
UniProtKB P56524 (Hs), Q6NZM9 (Mm)
Wikipedia HDAC4 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.5.1.98

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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 7.7 pKi 2
⤷ pKi 7.7 (Ki 2.05x10-8 M) [2]
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pKi 2
⤷ pKi 6.4 (Ki 3.8x10-7 M) [2]
givinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pKi 2
⤷ pKi 6.0 (Ki 1.05x10-6 M) [2]
trichostatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 pKi 2
⤷ pKi 5.8 (Ki 1.4x10-6 M) [2]
dacinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pKi 2
⤷ pKi 5.7 (Ki 2.25x10-6 M) [2]
scriptaid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.1 pKi 2
⤷ pKi 5.1 (Ki 7.5x10-6 M) [2]
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 7.9 pEC50 7
⤷ pEC50 7.9 (EC50 1.2x10-8 M) [7]
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 7
⤷ pEC50 7.3 (EC50 5.2x10-8 M) [7]
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 7
⤷ pEC50 6.9 (EC50 1.15x10-7 M) [7]
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 9.2 pIC50 1
⤷ pIC50 9.2 (IC50 6.4x10-10 M) [1]
CUDC-101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 3
⤷ pIC50 7.9 (IC50 1.32x10-8 M) [3]
TMP269 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 8
⤷ pIC50 6.8 (IC50 1.57x10-7 M) [8]
santacruzamate A Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 9
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [9]
martinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 10
⤷ pIC50 5.7 (IC50 1.97x10-6 M) [10]
KA1010 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 4
⤷ pIC50 5.5 (IC50 3.072x10-6 M) [4]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tasquinimod Small molecule or natural product Hs Inhibition 7.5 – 8.0 pKd 6
⤷ pKd 7.5 – 8.0 (Kd 3x10-8 – 1x10-8 M) [6]
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Brachydactyly-mental retardation syndrome; BDMR
Synonyms: 2q37 microdeletion syndrome [Orphanet: ORPHA1001]
OMIM: 600430
Orphanet: ORPHA1001
General Comments
HDAC4 is a Class II 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. 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. Grozinger CM, Hassig CA, Schreiber SL. (1999) Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci USA, 96 (9): 4868-73. [PMID:10220385]

6. Isaacs JT, Antony L, Dalrymple SL, Brennen WN, Gerber S, Hammers H, Wissing M, Kachhap S, Luo J, Xing L et al.. (2013) Tasquinimod Is an Allosteric Modulator of HDAC4 survival signaling within the compromised cancer microenvironment. Cancer Res, 73 (4): 1386-99. [PMID:23149916]

7. 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]

8. Lobera M, Madauss KP, Pohlhaus DT, Wright QG, Trocha M, Schmidt DR, Baloglu E, Trump RP, Head MS, Hofmann GA et al.. (2013) Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol, 9 (5): 319-25. [PMID:23524983]

9. 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]

10. 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 4. Last modified on 16/07/2020. Accessed on 23/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2659.