Target Information

Target General Infomation
Target ID
T28887
Former ID
TTDR01337
Target Name
Histone Deacetylase 8
Gene Name
HDAC8
Synonyms
Histone deacetylase-8; HD8; HDAC8
Target Type
Research
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Function
Responsible 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, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. {ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473, ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:22885700}.
BioChemical Class
Carbon-nitrogen hydrolase
Target Validation
T28887
UniProt ID
Q9BY41
EC Number
EC 3.5.1.98
Sequence
MEEPEEPADSGQSLVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPK
VASMEEMATFHTDAYLQHLQKVSQEGDDDHPDSIEYGLGYDCPATEGIFDYAAAIGGATI
TAAQCLIDGMCKVAINWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLH
HGDGVEDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGIQDEKY
YQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIGKCLKYILQWQLATLI
LGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEFFTAYGPDYVLEITPSCRPDRNEPH
RIQQILNYIKGNLKHVV
Structure
1T64; 1T67; 1T69; 1VKG; 1W22; 2V5W; 2V5X; 3EW8; 3EWF; 3EZP; 3EZT; 3F06; 3F07; 3F0R; 3MZ3; 3MZ4; 3MZ6; 3MZ7; 3RQD; 3SFF; 3SFH; 4QA0; 4QA1; 4QA2; 4QA3; 4QA4; 4QA5; 4QA6; 4QA7
Inhibitor (E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one Drug Info [1]
2-(methylsulfonylthio)ethyl 2-propylpentanoate Drug Info [2]
4-Benzoylamino-N-hydroxy-benzamide Drug Info [3]
4-Butyrylamino-N-hydroxy-benzamide Drug Info [4]
4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info [5]
4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide Drug Info [6]
4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info [5]
4-Phenylbutyrohydroxamic acid Drug Info [7]
5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide Drug Info [8]
5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione Drug Info [2]
5-Mercapto-pentanoic acid phenylamide Drug Info [6]
6-(2-Bromo-acetylamino)-hexanoic acid phenylamide Drug Info [6]
6-(2-mercaptoacetamido)-N-phenylhexanamide Drug Info [9]
6-benzenesulfinylhexanoic acid hydroxamide Drug Info [10]
6-benzenesulfonylhexanoic acid hydroxamide Drug Info [10]
6-Mercapto-hexanoic acid phenylamide Drug Info [6]
6-Phenoxy-hexane-1-thiol Drug Info [6]
6-phenylsulfanylhexanoic acid hydroxamide Drug Info [10]
7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [1]
7-(Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one Drug Info [11]
7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [1]
7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info [1]
7-Mercapto-heptanoic acid benzothiazol-2-ylamide Drug Info [6]
7-Mercapto-heptanoic acid biphenyl-3-ylamide Drug Info [6]
7-Mercapto-heptanoic acid biphenyl-4-ylamide Drug Info [6]
7-Mercapto-heptanoic acid phenylamide Drug Info [6]
7-Mercapto-heptanoic acid pyridin-3-ylamide Drug Info [6]
7-Mercapto-heptanoic acid quinolin-3-ylamide Drug Info [6]
8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one Drug Info [1]
8-Mercapto-octanoic acid phenylamide Drug Info [6]
8-Oxo-8-phenyl-octanoic acid Drug Info [5]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide Drug Info [11]
9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one Drug Info [11]
9-mercapto-8-oxo-N-phenylnonanamide Drug Info [9]
Azithromycin-N-benzyltriazolylhexahydroxamic Acid Drug Info [12]
Azithromycin-N-benzyltriazolylnonahydroxamic Acid Drug Info [12]
Azithromycin-N-benzyltriazolyloctahydroxamic Acid Drug Info [12]
Azithromycinarylalkylhydroxamic Acid Drug Info [12]
Cyclostellettamine derivative Drug Info [13]
Desclasinose Azithromycinarylalkyl Hydroxamate Drug Info [12]
droxinostat Drug Info [14]
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide Drug Info [15]
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide Drug Info [15]
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide Drug Info [5]
N-(6-Hydroxycarbamoyl-hexyl)-benzamide Drug Info [5]
N-(6-Mercapto-hexyl)-benzamide Drug Info [6]
N-hydroxy-1-naphthamide Drug Info [16]
N-hydroxy-3-(naphthalen-1-yl)acrylamide Drug Info [16]
N-hydroxy-3-phenoxybenzamide Drug Info [16]
N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide Drug Info [3]
N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide Drug Info [3]
N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide Drug Info [3]
N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide Drug Info [3]
N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide Drug Info [3]
N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide Drug Info [3]
N-hydroxy-4-(naphthalen-1-yl)benzamide Drug Info [16]
N-Hydroxy-4-(pentanoylamino-methyl)-benzamide Drug Info [4]
N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide Drug Info [4]
N-Hydroxy-4-phenylacetylamino-benzamide Drug Info [3]
NILTUBACIN Drug Info [7]
NMB-T-BMX-OS01 Drug Info [17]
Octanedioic acid bis-hydroxyamide Drug Info [7]
Octanedioic acid hydroxyamide pyridin-2-ylamide Drug Info [5]
Octanedioic acid hydroxyamide pyridin-4-ylamide Drug Info [5]
PCI-34051 Drug Info [17]
PSAMMAPLIN A Drug Info [11]
S-2,9-dioxo-9-(phenylamino)nonyl ethanethioate Drug Info [9]
ST-2986 Drug Info [18]
ST-2987 Drug Info [18]
ST-3050 Drug Info [18]
Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester Drug Info [6]
Pathways
KEGG Pathway Alcoholism
Viral carcinogenesis
PANTHER Pathway Wnt signaling pathway
Pathway Interaction Database 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
HDACs deacetylate histones
WikiPathways Integrated Pancreatic Cancer Pathway
Neural Crest Differentiation
Cell Cycle
References
REF 1Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
REF 2Bioorg 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 3J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
REF 4J 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 5J 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 6J 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 7Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.Chemical phylogenetics of histone deacetylases.
REF 8Bioorg 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 9J Med Chem. 2008 Mar 27;51(6):1505-29. Epub 2008 Feb 5.Histone deacetylase inhibitors: from bench to clinic.
REF 10J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
REF 11J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
REF 12J Med Chem. 2009 Jan 22;52(2):456-68.Non-peptide macrocyclic histone deacetylase inhibitors.
REF 13Bioorg 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 14Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56.
REF 15Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
REF 16Bioorg Med Chem Lett. 2007 May 15;17(10):2874-8. Epub 2007 Feb 25.Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors.
REF 17(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. (Target id: 2619).
REF 18Bioorg 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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