Therapeutic Targets Database
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TTD Target ID: TTDS00095

Target Information
NameHistone deacetylase 1    
Type of targetSuccessful target    
SynonymsHDAC1    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1]
Proliferative diseases[1]
Prostate cancer (hormone refractory)
[ICD9: 140-229, 185   ICD10: C00-C96, C61]
[2][3]
Drug(s)RomidepsinApprovedCutaneous T cell lymphoma[4]
VorinostatApprovedCutaneous T-cell lymphoma[5][6][7]
NVP-LAQ824Phase IIISevere Mood Disorders[8]
RomidepsinPhase IIIRenal cell carcinoma, hormone refractory prostate cancer, AML, muliple myeloma[9][7]
TacedinalinePhase IIICancers[9][7]
ITF2357Phase IIMyelofibrosis, Essential thrombocythemia, Polycythemia?vera[10][11]
MS-275Phase IIMelanoma, Prostate, Lung and Colorectal Cancer[12][13][9][14]
PDX-101Phase IICancers[9]
PXD101Phase IIBladder Cancer, Ovarian Cancer, Cutaneous T-Cell Lymphoma, Mesothelioma[15][16][17][7]
PanobinostatPhase IIPrimary Myelofibrosis, Post-Polycythemia Vera, Post-Essential Thrombocytopenia, Cutaneous T cell-lymphomas, Multiple myeloma[5][18][9][7]
PhenylbutyratePhase IIUrea cycle disorders[19]
ResminostatPhase IIHepatocellular carcinoma[20]
RomidepsinPhase IIPeripheral T-Cell Lymphoma[7][21]
SNDX-275Phase IIHodgkin's Lymphoma, Multiple myeloma[11]
Sodium butyratePhase IIRefractory sickle cell ulcers[7][22]
PXD101Phase I/IIMyeloid Leukemia, Liver Cancer, Sarcoma[15][16][17][7]
SB-623Phase I/IIStroke[9]
PXD101Phase IbColorectal Cancer[15][16][17][7]
PXD101Phase IMyelodysplastic Syndrome, Solid Tumors[15][16][17][7]
PyroxamidePhase ICancers[9][7]
AN-9Terminated in Phase IIMalignant Melanoma[7]
LAQ824Discontinued in Phase IGeneral leukaemia cancer[7]
MGCD-0103Terminated in Phase II Acute Myelogenous Leukemia[5][9][7]
NVP-LAQ824Discontinued in Phase I/IIGeneral leukaemia cancer[9]
4SC-202PreclinicalCancer[20]
CHAP-15PreclinicalCancers[9]
ChlamydocinPreclinicalCancers[9]
Depudecin PreclinicalCancers[9][7]
FFF1PreclinicalCancers[9]
FFF2PreclinicalCancers[9]
FFF3PreclinicalCancers[9]
FFF4PreclinicalCancers[9]
HC-ToxinPreclinicalCancers[9]
HDAC-42PreclinicalCancers[9]
JNS-16241199PreclinicalCancers[9]
M-carboxycinnamic acid bishydroxamidePreclinicalCancers[9][7]
OxamflatinPreclinicalCancers[9][7]
RG2833PreclinicalCancer[23]
SB-6241PreclinicalCancers[9]
SB-639PreclinicalCancers[9]
SK-7041PreclinicalCancers[9][7]
SK-7068PreclinicalCancers[9][7]
ScriptaidPreclinicalCancers[9][19][7]
BioChemical ClassHydrolases acting on carbon-nitrogen bonds    
PathwayCell cycle
Chronic myeloid leukemia
Huntington's disease
Notch signaling pathway
Pathways in cancer
UniProt IDQ13547
PDB Structure1TYI.    
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.    
SequenceMAQTQGTRRKVCYYYDGDVGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKAN AEEMTKYHSDDYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVAS AVKLNKQQTDIAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHG DGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNYPLRDGIDDESYEAI FKPVMSKVMEMFQPSAVVLQCGSDSLSGDRLGCFNLTIKGHAKCVEFVKSFNLPMLMLGG GGYTIRNVARCWTYETAVALDTEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTNEYLE KIKQRLFENLRMLPHAPGVQMQAIPEDAIPEESGDEDEDDPDKRISICSSDKRIACEEEF SDSEEEGEGGRKNSSNFKKAKRVKTEDEKEKDPEEKKEVTEEEKTKEEKPEAKGVKEEVK LA
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor4SC-202[20]
6-Phenoxy-hexane-1-thiol[24]
6-phenylsulfanylhexanoic acid hydroxamide[25]
ADS-100380[26]
ADS-102550[26]
AN-9[7]
AZUMAMIDE B[27]
AZUMAMIDE C[27]
AZUMAMIDE E[27]
Azithromycin-N-benzyltriazolyldecahydroxamic Acid[28]
Azithromycin-N-benzyltriazolylhexahydroxamic Acid[28]
Azithromycin-N-benzyltriazolylnonahydroxamic Acid[28]
Azithromycin-N-benzyltriazolyloctahydroxamic Acid[28]
Azithromycinarylalkylhydroxamic Acid[28]
CHAP-15[9]
CI-994[29]
Chlamydocin[9]
Cyclostellettamine derivative[30]
DEPUDECIN[29]
Depudecin [9][7]
Desclasinose Azithromycinarylalkyl Hydroxamate[28]
FFF1[9]
FFF2[9]
FFF3[9]
FFF4[9]
HC-Toxin[9]
HDAC-42[9]
ITF2357[10][11]
JNS-16241199[9]
LAQ824[7]
LARGAZOLE[31]
M-carboxycinnamic acid bishydroxamide[9][7]
MGCD-0103[5][9][7]
MS-275[12][13][9][14]
NSC-746457[32]
NVP-LAQ824[8]
NVP-LAQ824[9]
Octanedioic acid bis-hydroxyamide[33]
Octanedioic acid hydroxyamide pyridin-2-ylamide[34]
Octanedioic acid hydroxyamide pyridin-4-ylamide[34]
Oxamflatin[9][7]
PDX-101[9]
PSAMMAPLIN A[35]
PXD101[15][16][17][7]
Panobinostat[5][18][9][7]
Phenylbutyrate[19]
Pyroxamide[9][7]
RG2833[23]
Resminostat[20]
Romidepsin[7][21]
Romidepsin[9][7]
Romidepsin[4]
SB-623[9]
SB-6241[9]
SB-639[9]
SK-683[36]
SK-7041[9][7]
SK-7068[9][7]
SNDX-275[11]
ST-2986[37]
ST-2987[37]
ST-3050[37]
Scriptaid[9][19][7]
Sodium butyrate[7][22]
Tacedinaline[9][7]
Thioacetic acid S- (6-phenylcarbamoyl-hexyl) ester[24]
Trichostatin[1]
Vorinostat[5][6][7]
gymnochrome E[38]
MultitargetITF2357[10][11]
Phenylbutyrate[19]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Identification of novel isoform-selective inhibitors within class I histone deacetylases. J Pharmacol Exp Ther. 2003 Nov;307(2):720-8. Epub 2003 Sep 15. To Reference
Ref 2Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha. Int J Cancer. 2003 Nov 10;107(3):353-8. To Reference
Ref 3Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate. 2004 May 1;59(2):177-89. To Reference
Ref 4Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. To Reference
Ref 5Protein methyltransferases as a target class for drug discovery. Nat Rev Drug Discov. 2009 Sep;8(9):724-32. To Reference
Ref 6Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties. J Med Chem. 2009 Jun 11;52(11):3453-6. To Reference
Ref 7Nat Rev Drug Discov. 2006 Sep;5(9):769-84.Anticancer activities of histone deacetylase inhibitors. To Reference
Ref 8Blood. 2003 Oct 1;102(7):2615-22. Epub 2003 Jun 19.NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. To Reference
Ref 9Histone 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 10Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Jun 24. [Epub ahead of print] To Reference
Ref 11Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. To Reference
Ref 12Transcriptional induction of GRP78/BiP by histone deacetylase inhibitors and resistance to histone deacetylase inhibitor-induced apoptosis. Mol Cancer Ther. 2009 May 5. [Epub ahead of print] To Reference
Ref 13Induction of Foxp3+ regulatory T cells with histone deacetylase inhibitors. Cell Immunol. 2009;257(1-2):97-104. Epub 2009 Apr 8. To Reference
Ref 14Cell Res. 2007 Mar;17(3):195-211.HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics. To Reference
Ref 15Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo. Br J Cancer. 2009 Mar 10;100(5):758-63. To Reference
Ref 16The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs. 2009 Jan 27. [Epub ahead of print] To Reference
Ref 17Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol. 2009 Jan;4(1):97-101. To Reference
Ref 18Emerging drugs in cutaneous T cell lymphoma. Expert Opin Emerg Drugs. 2008 Jun;13(2):345-61. To Reference
Ref 19Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. To Reference
Ref 202011 Pipeline of 4SC AG. To Reference
Ref 21Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother Pharmacol. 2001 Aug;48 Suppl 1:S20-6. To Reference
Ref 22Two 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
Ref 232011 Pipeline of Repligen. To Reference
Ref 24J 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 25J 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 26Bioorg Med Chem Lett. 2007 Jan 15;17(2):363-9. Epub 2006 Oct 24.Identification and optimisation of a series of substituted 5-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors. To Reference
Ref 27Bioorg Med Chem Lett. 2008 May 1;18(9):2982-4. Epub 2008 Mar 21.Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells. To Reference
Ref 28J Med Chem. 2009 Jan 22;52(2):456-68.Non-peptide macrocyclic histone deacetylase inhibitors. To Reference
Ref 29Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.Chemical phylogenetics of histone deacetylases. To Reference
Ref 30Bioorg 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 31J Med Chem. 2010 Jun 24;53(12):4654-67.Synthesis and biological characterization of the histone deacetylase inhibitor largazole and C7- modified analogues. To Reference
Ref 32J Med Chem. 2008 Dec 11;51(23):7417-27.Histone deacetylase inhibitors through click chemistry. To Reference
Ref 33J Med Chem. 2002 Jul 18;45(15):3296-309.Structure-activity relationships on phenylalanine-containing inhibitors of histone deacetylase: in vitro enzyme inhibition, induction of differentiation, and inhibition of proliferation in Friend leukemic cells. To Reference
Ref 34J 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 35J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors. To Reference
Ref 36J Med Chem. 2004 Jun 17;47(13):3409-17.On the function of the 14 A long internal cavity of histone deacetylase-like protein: implications for the design of histone deacetylase inhibitors. To Reference
Ref 37Bioorg 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 38J Nat Prod. 2010 Apr 23;73(4):712-5.Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii. To Reference



 

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Professor in Department of Pharmacy
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