Target General Infomation
Target ID
T65755
Former ID
TTDC00297
Target Name
Histone deacetylase
Synonyms
HD; HDAC
Target Type
Successful
Disease Autoimmune diabetes [ICD10: E08-E13]
Cutaneous T-cell lymphoma [ICD9: 202.1, 202.2; ICD10: C84.0, C84.1]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Epilepsy [ICD10: G40]
HIV-1 infection [ICD9: 001-139, 042; ICD10: B20-B24]
Keratosis [ICD10: L57.0]
Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86]
Multiple myeloma [ICD9: 203; ICD10: C90]
Myelodysplastic syndrome; Myelofibrosis [ICD9:238.7, 208.9, 289.83, 709.2; ICD10: D46, C94.4, D47.4]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Rhinovirus infection [ICD10: J20.6?]
Spinal muscular atrophy [ICD9: 335.0-335.1; ICD10: G00-G99]
Function
Responsible for the deacetylation of lysine residues on the n-terminal part of the core histones (H2a, H2b, H3 and H4). Histone deacetylation givesa tag for epigenetic repression and plays an important role in transcriptional regulation.
BioChemical Class
Carbon-nitrogen hydrolase
Target Validation
T65755
EC Number
EC 3.5.1.-
Drugs and Mode of Action
Drug(s) Sodium phenylbutyrate Drug Info Approved Spinal muscular atrophy [522122]
Valproic Acid Drug Info Approved Epilepsy [536447], [542039], [551871]
CMS-024-02 Drug Info Phase 3 Cancer [523721]
Abexinostat Drug Info Phase 2 Cancer [543092], [548180]
APH-0812 Drug Info Phase 2 HIV-1 infection [526936], [528914]
DAC-060 Drug Info Phase 2 Keratosis [548990]
JNJ-26481585 Drug Info Phase 2 Cancer [530481], [542523]
PDX-101 Drug Info Phase 2 Cancer [533034]
Pracinostat Drug Info Phase 2 Myelodysplastic syndrome; Myelofibrosis [543091], [548531]
Rocilinostat Drug Info Phase 2 Multiple myeloma [549121]
ACY-1215 Drug Info Phase 1/2 Autoimmune diabetes [524684], [542040]
CG-200745 Drug Info Phase 1 Cancer [523222]
CT-200 Drug Info Phase 1 Cancer [548651]
CXD-101 Drug Info Phase 1 Cancer [524509]
GSK311739 Drug Info Phase 1 Rhinovirus infection [551509]
GSK3117391 Drug Info Phase 1 Rheumatoid arthritis [550970]
SHAPE Drug Info Phase 1 Lymphoma [550089]
SHP-141 Drug Info Phase 1 Cutaneous T-cell lymphoma [523985]
CS-00028 Drug Info Preclinical Cancer [548010]
MKC-1313 Drug Info Terminated Cancer [548343]
Inhibitor (E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one Drug Info [526871]
2,2-bis(3-fluorophenyl)-N-hydroxyacetamide Drug Info [530327]
2,2-bis(4-chlorophenyl)-N-hydroxyacetamide Drug Info [530327]
2,2-bis(4-fluorophenyl)-N-hydroxyacetamide Drug Info [530327]
2-(methylsulfonylthio)ethyl 2-propylpentanoate Drug Info [529333]
4-Benzoylamino-N-hydroxy-benzamide Drug Info [527691]
4-Butyrylamino-N-hydroxy-benzamide Drug Info [526922]
4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info [526266]
4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide Drug Info [527439]
4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info [526266]
4-Phenylbutyrohydroxamic acid Drug Info [530700]
5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide Drug Info [527056]
5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione Drug Info [529333]
5-Mercapto-pentanoic acid phenylamide Drug Info [527439]
6-(2-Bromo-acetylamino)-hexanoic acid phenylamide Drug Info [527439]
6-benzenesulfinylhexanoic acid hydroxamide Drug Info [527980]
6-benzenesulfonylhexanoic acid hydroxamide Drug Info [527980]
6-Mercapto-hexanoic acid phenylamide Drug Info [527439]
6-Phenoxy-hexane-1-thiol Drug Info [527439]
6-phenylsulfanylhexanoic acid hydroxamide Drug Info [527980]
7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [526871]
7-(Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one Drug Info [526878]
7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [526871]
7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [526871]
7-Mercapto-heptanoic acid benzothiazol-2-ylamide Drug Info [527439]
7-Mercapto-heptanoic acid biphenyl-3-ylamide Drug Info [527439]
7-Mercapto-heptanoic acid biphenyl-4-ylamide Drug Info [527439]
7-Mercapto-heptanoic acid phenylamide Drug Info [527439]
7-Mercapto-heptanoic acid pyridin-3-ylamide Drug Info [527439]
7-Mercapto-heptanoic acid quinolin-3-ylamide Drug Info [527439]
8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one Drug Info [526871]
8-Mercapto-octanoic acid phenylamide Drug Info [527439]
8-Oxo-8-phenyl-octanoic acid Drug Info [526266]
8-Oxo-8-phenyl-octanoic acid hydroxyamide Drug Info [526878]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide Drug Info [526878]
9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one Drug Info [526878]
APH-0812 Drug Info [526936], [528914]
Apicidin Drug Info [535634], [536272], [536509]
Azelaic bishydroxamic acid Drug Info [536272]
CG-1521 Drug Info [536272]
CG-200745 Drug Info [533181]
CHAP1 Drug Info [535274], [536509]
CHAP31 Drug Info [535274], [536509]
CT-200 Drug Info [549783]
CXD-101 Drug Info [530566]
Cyclostellettamine derivative Drug Info [527058]
DAC-060 Drug Info [544228]
LBH539 Drug Info [537114]
MKC-1313 Drug Info [551674]
N-(2,3-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(2,4-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(2,5-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(2,6-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(2-amino-5-(thiophen-2-yl)phenyl)nicotinamide Drug Info [529767]
N-(2-aminophenyl)-4-methoxybenzamide Drug Info [529104]
N-(2-aminophenyl)nicotinamide Drug Info [529767]
N-(2-Ethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide Drug Info [527500]
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide Drug Info [527500]
N-(3,4-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(3,5-Dimethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(3-Ethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(4-aminobiphenyl-3-yl)nicotinamide Drug Info [529767]
N-(4-Ethylphenyl)-N'-hydroxyoctanediamide Drug Info [530704]
N-(5-Hydroxycarbamoyl-pentyl)-4-methoxy-benzamide Drug Info [525643]
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide Drug Info [526266]
N-(5-Hydroxycarbamoyl-pentyl)-benzamide Drug Info [525643]
N-(6-Hydroxycarbamoyl-hexyl)-benzamide Drug Info [526266]
N-(6-Mercapto-hexyl)-benzamide Drug Info [527439]
N-hydroxy-2,2-diphenylacetamide Drug Info [530327]
N-hydroxy-2,2-diphenylpropanamide Drug Info [530327]
N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide Drug Info [527691]
N-Hydroxy-4-(pentanoylamino-methyl)-benzamide Drug Info [526922]
N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide Drug Info [526922]
N-Hydroxy-4-phenylacetylamino-benzamide Drug Info [527691]
N-hydroxy-9,10-dihydroanthracene-9-carboxamide Drug Info [530327]
N-hydroxy-9H-xanthene-9-carboxamide Drug Info [530327]
N-Hydroxy-N'-(2-methylphenyl)octanediamide Drug Info [530704]
N-Hydroxy-N'-(3-methylphenyl)octanediamide Drug Info [530704]
N-Hydroxy-N'-(4-methoxyphenyl)octanediamide Drug Info [530704]
N-Hydroxy-N'-(4-methylphenyl)octanediamide Drug Info [530704]
N1-(biphenyl-4-yl)-N8-hydroxyoctanediamide Drug Info [530106]
Octanedioic acid bis-hydroxyamide Drug Info [530700]
Octanedioic acid hydroxyamide pyridin-2-ylamide Drug Info [526266]
Octanedioic acid hydroxyamide pyridin-4-ylamide Drug Info [526266]
PSAMMAPLIN A Drug Info [526878]
Rocilinostat Drug Info [550471]
SHAPE Drug Info [550090]
Sodium phenylbutyrate Drug Info [530995], [551871]
ST-2986 Drug Info [530016]
ST-2987 Drug Info [530016]
ST-3050 Drug Info [530016]
ST-5732 Drug Info [530067]
Suberic bishydroxamic acid Drug Info [536272]
Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester Drug Info [527439]
Trapoxin Drug Info [535274]
Trichostatin A Drug Info [535661], [536509], [537490]
Trifluoromethylketone Drug Info [536272]
Valproic Acid Drug Info [535221], [536272], [537490], [537523], [537552]
Modulator Abexinostat Drug Info [533112]
ACY-1215 Drug Info [544487]
CMS-024-02 Drug Info [550907]
GSK311739 Drug Info [550994]
GSK3117391 Drug Info [544203]
JNJ-26481585 Drug Info [542523]
PDX-101 Drug Info [1572591]
Pracinostat Drug Info [543091]
SHP-141 Drug Info [550476]
Antagonist CS-00028 Drug Info [551918]
References
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Ref 523721ClinicalTrials.gov (NCT01489566) Study of Tyroserleutide for Injection in Hepatocellular Carcinoma (HCC) Patients. U.S. National Institutes of Health.
Ref 523985ClinicalTrials.gov (NCT01646567) SHP-141C in Plaque Type Psoriasis. U.S. National Institutes of Health.
Ref 524509ClinicalTrials.gov (NCT01977638) Phase 1 Trial of CXD101 in Patients With Advanced Cancer. U.S. National Institutes of Health.
Ref 524684ClinicalTrials.gov (NCT02091063) ACY-1215 for Relapsed/Refractory Lymphoid Malignancies. U.S. National Institutes of Health.
Ref 526936Bryostatin-1: a novel PKC inhibitor in clinical development. Cancer Invest. 2003;21(6):924-36.
Ref 528914Targeting the protein kinase C family: are we there yet. Nat Rev Cancer. 2007 Jul;7(7):554-62.
Ref 530481JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51.
Ref 533034A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811-9.
Ref 536447Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
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Ref 542040(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7010).
Ref 542523(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7503).
Ref 543091(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8365).
Ref 543092(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8366).
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Ref
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Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 526922J Med Chem. 2004 Jan 15;47(2):467-74.Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors.
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Ref 527056Bioorg Med Chem Lett. 2004 May 17;14(10):2477-81.Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides.
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Ref 527500Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 527980J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
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Ref 529104J Med Chem. 2007 Nov 15;50(23):5543-6. Epub 2007 Oct 17.Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity.
Ref 529333Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7. Epub 2008 Feb 8.New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity.
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Ref 537523Histone Deacetylase 2 is a Key Regulator of Diabetes and Transforming Growth Factor-{beta}1-Induced Renal Injury. Am J Physiol Renal Physiol. 2009 Jun 24.
Ref 537552Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One. 2009 Jun 30;4(6):e6086.
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Ref 543091(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8365).
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Ref 544487Promising therapies in multiple myeloma. Blood. 2015 July 16; 126(3): 300-310.
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