Therapeutic Targets Database
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TTD Target ID: TTDC00297

Target Information
NameHistone deacetylase    
Type of targetSuccessful target    
SynonymsHD    
HDAC    
DiseaseAcute myeloid leukemia
[ICD9: 205.0   ICD10: C92.0]
[1]
Cancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[2][3]
Hematologic malignancies
[ICD9: 200-209   ICD10: C81-C96]
[4]
Drug(s)Valproic AcidApprovedEpilepsy, psychiatric disorders[5][6][7][8][9]
AbexinostatPhase IIFollicular lymphoma, mantle cell lymphoma
JNJ-26481585Phase IICutaneous T-cell lymphoma
PracinostatPhase IIMyelodysplastic syndromes (see also myeloproliferative)
PracinostatPhase IIMyelofibrosis (see also leukemia)
ACY-1215Phase I/IIMyeloma
AbexinostatPhase I/IILymphoma
AbexinostatPhase I/IISarcoma (see also lymphoma)
CUDC-907Phase IDiffuse large B-cell lymphoma (see also myeloma)
CUDC-907Phase IMyeloma (see also lymphoma)
HBI-8000Phase ILymphoma
SHP-141Phase ICutaneous T-cell lymphoma
BioChemical ClassHydrolases acting on carbon-nitrogen bonds    
EC NumberEC 3.5.1.-
FunctionResponsible for the deacetylation of lysine residues on the n-terminal part of the core histones (H2a, H2b, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation.    
SequenceMDTGGNSLASGPDGVKRKVCYFYDPEVGNYYYGQGHPMKPHRIRMTHALLAHYGLLQHMQ VLKPFPARDRDLCRFHADDYVSFLRSITPETQQDQIRQLKRFNVGEDCPVFDGLYSFCQT YAGGSVGGSVKLNHGLCDIAINWAGGLHHAKKCEASGFCYVNDIVLAILELLKQHERVLY VDIDIHHGDGVEEAFYATDRVMTVSFHKFGDYFPGTGHIQDIGYGSGKYYSLNVPLDDGI DDESYHLLFKPIMGKVMEIFRPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVKFMRSFN VPLLLLGGGGYTIRNVARCWCYETGVALGVEVEDKMPEHEYYEYFGPDYTLHVAPSNMEN KNSRQMLEEIRNDLLHNLSKLQHAPSVPFQERPPDTETPEVDEDQEDGDKRWDPDSDMDV DDDRKPIPSRVKREAVEPDTKDKDGLKGIMERGKGCEVEVDESGSTKVTGVNPVGVEEAS VKMEEEGTNKGGAEQAFPPKT
Related US Patent6,495,719
6,511,990
6,541,661
6,552,065
6,638,530
Target ValidationClick to Find Target Validation Information.    
Inhibitor (E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one[10]
2,2-bis (3-fluorophenyl)-N-hydroxyacetamide[11]
2,2-bis (4-chlorophenyl)-N-hydroxyacetamide[11]
2,2-bis (4-fluorophenyl)-N-hydroxyacetamide[11]
2- (methylsulfonylthio)ethyl 2-propylpentanoate[12]
4-Benzoylamino-N-hydroxy-benzamide[13]
4-Butyrylamino-N-hydroxy-benzamide[14]
4-Chloro-N- (5-hydroxycarbamoyl-pentyl)-benzamide[15]
4-Dimethylamino-N- (6-mercapto-hexyl)-benzamide[16]
4-Hydroxy-N- (5-hydroxycarbamoyl-pentyl)-benzamide[15]
4-Phenylbutyrohydroxamic acid[17]
5- (4-Chloro-phenyl)-pentanoic acid hydroxyamide[18]
5- (4-hydroxyphenyl)-3H-1,2-dithiole-3-thione[12]
5-Mercapto-pentanoic acid phenylamide[16]
6- (2-Bromo-acetylamino)-hexanoic acid phenylamide[16]
6-Mercapto-hexanoic acid phenylamide[16]
6-Phenoxy-hexane-1-thiol[16]
6-benzenesulfinylhexanoic acid hydroxamide[19]
6-benzenesulfonylhexanoic acid hydroxamide[19]
6-phenylsulfanylhexanoic acid hydroxamide[19]
7- (Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one[10]
7- (Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one[20]
7- (Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one[10]
7- (Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one[10]
7-Mercapto-heptanoic acid benzothiazol-2-ylamide[16]
7-Mercapto-heptanoic acid biphenyl-3-ylamide[16]
7-Mercapto-heptanoic acid biphenyl-4-ylamide[16]
7-Mercapto-heptanoic acid phenylamide[16]
7-Mercapto-heptanoic acid pyridin-3-ylamide[16]
7-Mercapto-heptanoic acid quinolin-3-ylamide[16]
8- (Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one[10]
8-Mercapto-octanoic acid phenylamide[16]
8-Oxo-8-phenyl-octanoic acid[15]
8-Oxo-8-phenyl-octanoic acid hydroxyamide[20]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide[20]
9- (Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one[20]
Apicidin[21][8][22]
Azelaic bishydroxamic acid[8]
CG-1521[8]
CHAP1[21][23]
CHAP31[21][23]
CI-994[17]
Cyclostellettamine derivative[24]
DEPUDECIN[17]
LBH539[25]
N- (2,3-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (2,4-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (2,5-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (2,6-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (2-Ethylphenyl)-N'-hydroxyoctanediamide[26]
N- (2-Mercapto-ethyl)-N'-phenyl-oxalamide[27]
N- (2-Mercapto-ethyl)-N'-phenyl-succinamide[27]
N- (2-amino-5-[28]
N- (2-aminophenyl)-4-methoxybenzamide[29]
N- (2-aminophenyl)nicotinamide[28]
N- (3,4-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (3,5-Dimethylphenyl)-N'-hydroxyoctanediamide[26]
N- (3-Ethylphenyl)-N'-hydroxyoctanediamide[26]
N- (4-Ethylphenyl)-N'-hydroxyoctanediamide[26]
N- (4-aminobiphenyl-3-yl)nicotinamide[28]
N- (5-Hydroxycarbamoyl-pentyl)-4-methoxy-benzamide[30]
N- (5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide[15]
N- (5-Hydroxycarbamoyl-pentyl)-benzamide[30]
N- (6-Hydroxycarbamoyl-hexyl)-benzamide[15]
N- (6-Mercapto-hexyl)-benzamide[16]
N-Hydroxy-4- ([13]
N-Hydroxy-4- ([13]
N-Hydroxy-4- (2-phenyl-butyrylamino)-benzamide[13]
N-Hydroxy-4- (3-phenyl-propionylamino)-benzamide[13]
N-Hydroxy-4- (4-phenyl-butyrylamino)-benzamide[13]
N-Hydroxy-4- (5-phenyl-pentanoylamino)-benzamide[13]
N-Hydroxy-4- (pentanoylamino-methyl)-benzamide[14]
N-Hydroxy-4- (phenylacetylamino-methyl)-benzamide[14]
N-Hydroxy-4-phenylacetylamino-benzamide[13]
N-Hydroxy-N'- (2-methylphenyl)octanediamide[26]
N-Hydroxy-N'- (3-methylphenyl)octanediamide[26]
N-Hydroxy-N'- (4-methoxyphenyl)octanediamide[26]
N-Hydroxy-N'- (4-methylphenyl)octanediamide[26]
N-hydroxy-2,2-diphenylacetamide[11]
N-hydroxy-2,2-diphenylpropanamide[11]
N-hydroxy-9,10-dihydroanthracene-9-carboxamide[11]
N-hydroxy-9H-xanthene-9-carboxamide[11]
N1- (biphenyl-4-yl)-N8-hydroxyoctanediamide[31]
Octanedioic acid hydroxyamide pyridin-2-ylamide[15]
Octanedioic acid hydroxyamide pyridin-4-ylamide[15]
PSAMMAPLIN A[20]
ST-2986[32]
ST-2987[32]
ST-3050[32]
ST-5732[33]
Suberic bishydroxamic acid[8]
Suberohydroxamic acid[17]
Thioacetic acid S- (6-phenylcarbamoyl-hexyl) ester[16]
Trapoxin[23]
Trapoxin A[8]
Trichostatin A[7][21][34]
Trifluoromethylketone[8]
Valproic Acid[5][6][7][8][9]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Analysis and identification of transcriptional repression domain of ETO. Zhonghua Xue Ye Xue Za Zhi. 2003 Jan;24(1):10-3. To Reference
Ref 2Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs. 2002 Jan;13(1):1-13. To Reference
Ref 3Quantitative structure-activity relationship study of histone deacetylase inhibitors. Curr Med Chem Anticancer Agents. 2004 May;4(3):273-99. To Reference
Ref 4Histone deacetylases as therapeutic targets in hematologic malignancies. Curr Opin Hematol. 2002 Jul;9(4):322-32. To Reference
Ref 5Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One. 2009 Jun 30;4(6):e6086. To Reference
Ref 6Histone 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. [Epub ahead of print] To Reference
Ref 7Histone deacetylase inhibitors induce apoptosis, histone hyperacetylation and up-regulation of gene transcription in Schistosoma mansoni. Mol Biochem Parasitol. 2009 Jun 16. [Epub ahead of print] To Reference
Ref 8Nat Rev Drug Discov. 2006 Sep;5(9):769-84.Anticancer activities of histone deacetylase inhibitors. To Reference
Ref 9The new generation of GABA enhancers. Potential in the treatment of epilepsy. CNS Drugs. 2001;15(5):339-50. To Reference
Ref 10Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase. To Reference
Ref 11Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors. To Reference
Ref 12Bioorg 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. To Reference
Ref 13J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. To Reference
Ref 14J 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. To Reference
Ref 15J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates. To Reference
Ref 16J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates. To Reference
Ref 17Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.Chemical phylogenetics of histone deacetylases. To Reference
Ref 18Bioorg 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. To Reference
Ref 19J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides. To Reference
Ref 20J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors. To Reference
Ref 21Histone deacetylase inhibitors in cancer therapy: latest developments, trends and medicinal chemistry perspective. Anticancer Agents Med Chem. 2007 Sep;7(5):576-92. To Reference
Ref 22Apicidin, a histone deacetylase inhibitor, induces differentiation of HL-60 cells. Cancer Lett. 2003 Jan 28;189(2):197-206. To Reference
Ref 23Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother Pharmacol. 2001 Aug;48 Suppl 1:S20-6. To Reference
Ref 24Bioorg 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. To Reference
Ref 25Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. To Reference
Ref 26J Med Chem. 2010 Mar 11;53(5):1937-50.Biological and biophysical properties of the histone deacetylase inhibitor suberoylanilide hydroxamic acid are affected by the presence of short alkyl groups on the phenyl ring. To Reference
Ref 27Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. To Reference
Ref 28Bioorg 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). To Reference
Ref 29J 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. To Reference
Ref 30J Med Chem. 1999 Nov 4;42(22):4669-79.Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. To Reference
Ref 31Bioorg Med Chem Lett. 2009 Jun 1;19(11):3023-6. Epub 2009 Apr 20.Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on HDAC biology and antiproliferative activity. To Reference
Ref 32Bioorg 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. To Reference
Ref 33Bioorg Med Chem Lett. 2009 May 15;19(10):2840-3. Epub 2009 Mar 26.Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors. To Reference
Ref 34Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages. Blood. 2003 May 1;101(9):3451-9. Epub 2003 Jan 2. To Reference



 

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Professor in Department of Pharmacy
National University of Singapore, Singapore


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