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histone deacetylase 5

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Target id: 2660

Nomenclature: histone deacetylase 5

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 - 1122 17q21.31 HDAC5 histone deacetylase 5
Mouse - 1113 11 D Hdac5 histone deacetylase 5
Rat - 1113 10q32.1 Hdac5 histone deacetylase 5
Database Links Click here for help
Alphafold Q9UQL6 (Hs), Q9Z2V6 (Mm)
BRENDA 3.5.1.98
CATH/Gene3D 3.40.800.20
ChEMBL Target CHEMBL2563 (Hs), CHEMBL2768 (Mm)
Ensembl Gene ENSG00000108840 (Hs), ENSMUSG00000008855 (Mm), ENSRNOG00000020905 (Rn)
Entrez Gene 10014 (Hs), 15184 (Mm), 84580 (Rn)
Human Protein Atlas ENSG00000108840 (Hs)
KEGG Enzyme 3.5.1.98
KEGG Gene hsa:10014 (Hs), mmu:15184 (Mm), rno:84580 (Rn)
OMIM 605315 (Hs)
Pharos Q9UQL6 (Hs)
RefSeq Nucleotide NM_005474 (Hs), NM_001077696 (Mm), NM_053450 (Rn)
RefSeq Protein NP_005465 (Hs), NP_001071164 (Mm), NP_445902 (Rn)
UniProtKB Q9UQL6 (Hs), Q9Z2V6 (Mm)
Wikipedia HDAC5 (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
belinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKi 2
⤷ pKi 6.8 (Ki 1.75x10-7 M) [2]
trichostatin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pKi 2
⤷ pKi 6.6 (Ki 2.6x10-7 M) [2]
dacinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pKi 2
⤷ pKi 6.4 (Ki 4.2x10-7 M) [2]
romidepsin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.3 pKi 2
⤷ pKi 6.3 (Ki 5.5x10-7 M) [2]
givinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKi 2
⤷ pKi 6.2 (Ki 6x10-7 M) [2]
scriptaid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pKi 2
⤷ pKi 6.0 (Ki 1x10-6 M) [2]
vorinostat Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.4 pKi 2
⤷ pKi 5.4 (Ki 3.6x10-6 M) [2]
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 8.4 pIC50 1
⤷ pIC50 8.4 (IC50 3.69x10-9 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 1.14x10-8 M) [3]
pracinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 8
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [8]
TMP269 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 6
⤷ pIC50 7.0 (IC50 9.7x10-8 M) [6]
CHR-3996 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 7
⤷ pIC50 6.7 (IC50 2x10-7 M) [7]
martinostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 10
⤷ pIC50 6.4 (IC50 3.52x10-7 M) [10]
KA1010 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.0 pIC50 5
⤷ pIC50 6.0 (IC50 1.093x10-6 M) [5]
SS-208 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.2 pIC50 9
⤷ pIC50 5.2 (IC50 6.91x10-6 M) [9]
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hdac5+|Hdac5tm1Eno|Pkd2tm2Som Hdac5tm1Eno/Hdac5+,Pkd2tm2Som/Pkd2tm2Som
involves: 129/Sv * 129S2/SvPas * C57BL/6 * SJL		 MGI:1099818  MGI:1333784  MP:0003675 kidney cysts PMID: 20181743 
Hdac5tm1Eno|Pkd2tm2Som Hdac5tm1Eno/Hdac5tm1Eno,Pkd2tm2Som/Pkd2tm2Som
involves: 129/Sv * 129S2/SvPas * C57BL/6 * SJL		 MGI:1099818  MGI:1333784  MP:0006208 lethality throughout fetal growth and development PMID: 20181743 
General Comments
HDAC5 is a Class II histone deacetylase. This histone deacetylase can associate with at least 12 different proteins, including components of the NuRD and Sin3A repression complexes [4].

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. Downes M, Ordentlich P, Kao HY, Alvarez JG, Evans RM. (2000) Identification of a nuclear domain with deacetylase activity. Proc Natl Acad Sci USA, 97 (19): 10330-5. [PMID:10984530]

5. 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]

6. 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]

7. 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]

8. 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]

9. Shen S, Hadley M, Ustinova K, Pavlicek J, Knox T, Noonepalle S, Tavares MT, Zimprich CA, Zhang G, Robers MB et al.. (2019) Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models. J Med Chem, 62 (18): 8557-8577. [PMID:31414801]

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 5. Last modified on 16/07/2020. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2660.