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]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Cutaneous T-cell lymphoma [ICD9: 202.1, 202.2; ICD10: C84.0, C84.1]
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 523222ClinicalTrials.gov (NCT01226407) Examine Maximum Tolerated Dose and Pharmacokinetic and Pharmacodynamic Profile. U.S. National Institutes of Health.
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 548990Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031213)
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Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
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Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
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.
Ref 527058Bioorg Med Chem Lett. 2004 May 17;14(10):2617-20.Three new cyclostellettamines, which inhibit histone deacetylase, from a marine sponge of the genus Xestospongia.
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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.
Ref 529767Bioorg Med Chem Lett. 2008 Dec 1;18(23):6104-9. Epub 2008 Oct 14.SAR profiles of spirocyclic nicotinamide derived selective HDAC1/HDAC2 inhibitors (SHI-1:2).
Ref 530016Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9. Epub 2009 Feb 12.N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC)inhibitors.
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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 544228Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed. Correction in: volume 4 on page 1369.
Ref 544487Promising therapies in multiple myeloma. Blood. 2015 July 16; 126(3): 300-310.
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