Target Information
Target General Infomation | |||||
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Target ID |
T22274
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Former ID |
TTDNC00542
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Target Name |
Histone deacetylase 6
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Gene Name |
HDAC6
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Synonyms |
HD6; Histone deacetylase 6; HDAC6
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Target Type |
Clinical Trial
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Disease | Autoimmune diabetes [ICD10: E08-E13] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Multiple myeloma [ICD9: 203; ICD10: C90] | |||||
Function |
In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins andtarget them to the aggresome, facilitating their clearance by autophagy.
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BioChemical Class |
Carbon-nitrogen hydrolase
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Target Validation |
T35206
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UniProt ID | |||||
EC Number |
EC 3.5.1.98
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Sequence |
MTSTGQDSTTTRQRRSRQNPQSPPQDSSVTSKRNIKKGAVPRSIPNLAEVKKKGKMKKLG
QAMEEDLIVGLQGMDLNLEAEALAGTGLVLDEQLNEFHCLWDDSFPEGPERLHAIKEQLI QEGLLDRCVSFQARFAEKEELMLVHSLEYIDLMETTQYMNEGELRVLADTYDSVYLHPNS YSCACLASGSVLRLVDAVLGAEIRNGMAIIRPPGHHAQHSLMDGYCMFNHVAVAARYAQQ KHRIRRVLIVDWDVHHGQGTQFTFDQDPSVLYFSIHRYEQGRFWPHLKASNWSTTGFGQG QGYTINVPWNQVGMRDADYIAAFLHVLLPVALEFQPQLVLVAAGFDALQGDPKGEMAATP AGFAQLTHLLMGLAGGKLILSLEGGYNLRALAEGVSASLHTLLGDPCPMLESPGAPCRSA QASVSCALEALEPFWEVLVRSTETVERDNMEEDNVEESEEEGPWEPPVLPILTWPVLQSR TGLVYDQNMMNHCNLWDSHHPEVPQRILRIMCRLEELGLAGRCLTLTPRPATEAELLTCH SAEYVGHLRATEKMKTRELHRESSNFDSIYICPSTFACAQLATGAACRLVEAVLSGEVLN GAAVVRPPGHHAEQDAACGFCFFNSVAVAARHAQTISGHALRILIVDWDVHHGNGTQHMF EDDPSVLYVSLHRYDHGTFFPMGDEGASSQIGRAAGTGFTVNVAWNGPRMGDADYLAAWH RLVLPIAYEFNPELVLVSAGFDAARGDPLGGCQVSPEGYAHLTHLLMGLASGRIILILEG GYNLTSISESMAACTRSLLGDPPPLLTLPRPPLSGALASITETIQVHRRYWRSLRVMKVE DREGPSSSKLVTKKAPQPAKPRLAERMTTREKKVLEAGMGKVTSASFGEESTPGQTNSET AVVALTQDQPSEAATGGATLAQTISEAAIGGAMLGQTTSEEAVGGATPDQTTSEETVGGA ILDQTTSEDAVGGATLGQTTSEEAVGGATLAQTTSEAAMEGATLDQTTSEEAPGGTELIQ TPLASSTDHQTPPTSPVQGTTPQISPSTLIGSLRTLELGSESQGASESQAPGEENLLGEA AGGQDMADSMLMQGSRGLTDQAIFYAVTPLPWCPHLVAVCPIPAAGLDVTQPCGDCGTIQ ENWVCLSCYQVYCGRYINGHMLQHHGNSGHPLVLSYIDLSAWCYYCQAYVHHQALLDVKN IAHQNKFGEDMPHPH |
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Structure |
3C5K; 3GV4; 3PHD
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Drugs and Mode of Action | |||||
Inhibitor | (E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one | Drug Info | [526871] | ||
(S)-2-Amino-N-cyclopentyl-7-mercaptoheptanamide | Drug Info | [529093] | |||
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 | [526878] | |||
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-(9H-carbazol-9-yl)-N-hydroxyhexanamide | Drug Info | [531216] | |||
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] | |||
7-mercapto-N-(4-phenylthiazol-2-yl)heptanamide | Drug Info | [529093] | |||
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] | |||
compound 16 | Drug Info | [531216] | |||
compound 7d | Drug Info | [529889] | |||
Cyclo(-L-Am7(S2Py)-A2in-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Tic-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ph4-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ph5-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Phe-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Phg-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ser(Bzl)-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-Aib-L-Ser-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-D-2MePhe-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-D-A1in-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-L-2MePhe-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclo(-L-Am7(S2Py)-L-A1in-L-Ala-D-Pro-) | Drug Info | [529054] | |||
Cyclostellettamine derivative | Drug Info | [527058] | |||
droxinostat | Drug Info | [530619] | |||
IKH-25 | Drug Info | [543662] | |||
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide | Drug Info | [527500] | |||
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide | Drug Info | [527500] | |||
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide | Drug Info | [526878] | |||
N-(6-Hydroxycarbamoyl-hexyl)-benzamide | Drug Info | [526266] | |||
N-(6-Mercapto-hexyl)-benzamide | Drug Info | [527439] | |||
N-(biphenyl-3-yl)-6-(sulfamoylamino)hexanamide | Drug Info | [529866] | |||
N-(quinolin-3-yl)-6-(sulfamoylamino)hexanamide | Drug Info | [529866] | |||
N-(quinolin-6-yl)-6-(sulfamoylamino)hexanamide | Drug Info | [529866] | |||
N-(quinolin-8-yl)-6-(sulfamoylamino)hexanamide | Drug Info | [529866] | |||
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-phenyl-6-(sulfamoylamino)hexanamide | Drug Info | [529866] | |||
N-[5-(Formyl-hydroxy-amino)-pentyl]-benzamide | Drug Info | [526917] | |||
N1-(biphenyl-3-yl)-N8-hydroxyoctanediamide | Drug Info | [529866] | |||
N1-(biphenyl-4-yl)-N8-hydroxyoctanediamide | Drug Info | [530106] | |||
N1-hydroxy-N8-(4-phenylthiazol-2-yl)octanediamide | Drug Info | [530106] | |||
nexturastat A | Drug Info | [532053] | |||
NILTUBACIN | Drug Info | [530700] | |||
NQN-1 | Drug Info | [531683] | |||
Octanedioic acid bis-hydroxyamide | Drug Info | [526376] | |||
Octanedioic acid hydroxyamide pyridin-2-ylamide | Drug Info | [526266] | |||
Octanedioic acid hydroxyamide pyridin-4-ylamide | Drug Info | [526266] | |||
PSAMMAPLIN A | Drug Info | [526878] | |||
santacruzamate A | Drug Info | [532523] | |||
ST-2741 | Drug Info | [530067] | |||
ST-2986 | Drug Info | [530016] | |||
ST-2987 | Drug Info | [530016] | |||
ST-3050 | Drug Info | [530016] | |||
Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester | Drug Info | [527439] | |||
Tubacin | Drug Info | [536272], [537114] | |||
UCL-67022 | Drug Info | [543662] | |||
Modulator | ACY-1215 | Drug Info | [544487] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
Pathways | |||||
KEGG Pathway | Alcoholism | ||||
Viral carcinogenesis | |||||
Pathway Interaction Database | Signaling events mediated by HDAC Class II | ||||
Signaling events mediated by HDAC Class I | |||||
Reactome | NOTCH1 Intracellular Domain Regulates Transcription | ||||
Constitutive Signaling by NOTCH1 PEST Domain Mutants | |||||
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | |||||
Assembly of the primary cilium | |||||
WikiPathways | Ectoderm Differentiation | ||||
Neural Crest Differentiation | |||||
Cell Cycle | |||||
References | |||||
Ref 526266 | J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates. | ||||
Ref 526376 | J 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. | ||||
Ref 526871 | Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase. | ||||
Ref 526917 | Bioorg Med Chem Lett. 2004 Jan 19;14(2):449-53.Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group. | ||||
Ref 526922 | J 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. | ||||
Ref 527056 | Bioorg 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 527058 | Bioorg 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. | ||||
Ref 527439 | J 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. | ||||
Ref 527500 | Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. | ||||
Ref 527691 | J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. | ||||
Ref 527980 | J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides. | ||||
Ref 529054 | Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework. | ||||
Ref 529093 | J Med Chem. 2007 Nov 1;50(22):5425-38. Epub 2007 Oct 11.Design, synthesis, structure--selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors. | ||||
Ref 529333 | Bioorg 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 529866 | Bioorg Med Chem Lett. 2009 Jan 15;19(2):336-40. Epub 2008 Nov 27.Sulfamides as novel histone deacetylase inhibitors. | ||||
Ref 529889 | Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors. Bioorg Med Chem Lett. 2009 Feb 1;19(3):688-92. | ||||
Ref 530016 | Bioorg 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. | ||||
Ref 530067 | Bioorg 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. | ||||
Ref 530106 | Bioorg 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. | ||||
Ref 530619 | Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56. | ||||
Ref 530700 | Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.Chemical phylogenetics of histone deacetylases. | ||||
Ref 531216 | Bioorg Med Chem Lett. 2010 Dec 1;20(23):7067-70. Epub 2010 Oct 12.Inhibitors selective for HDAC6 in enzymes and cells. | ||||
Ref 531683 | A novel class of small molecule inhibitors of HDAC6. ACS Chem Biol. 2012 Feb 17;7(2):331-9. | ||||
Ref 532053 | Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J Med Chem. 2012 Nov 26;55(22):9891-9. | ||||
Ref 532523 | Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp. J Nat Prod. 2013 Nov 22;76(11):2026-33. | ||||
Ref 536272 | Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006 Sep;5(9):769-84. |
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