General Information of Drug Therapeutic Target (DTT) (ID: TTT6LFV)

DTT Name Histone deacetylase 8 (HDAC8)
Synonyms Histone deacetylase-8; HDACL1; HD8; CDA07
Gene Name HDAC8
DTT Type
Clinical trial target
[1]
BioChemical Class
Carbon-nitrogen hydrolase
UniProt ID
HDAC8_HUMAN
TTD ID
T28887
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.5.1.98
Sequence
MEEPEEPADSGQSLVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPK
VASMEEMATFHTDAYLQHLQKVSQEGDDDHPDSIEYGLGYDCPATEGIFDYAAAIGGATI
TAAQCLIDGMCKVAINWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLH
HGDGVEDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGIQDEKY
YQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIGKCLKYILQWQLATLI
LGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEFFTAYGPDYVLEITPSCRPDRNEPH
RIQQILNYIKGNLKHVV
Function
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. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
KEGG Pathway
Alcoholism (hsa05034 )
Viral carcinogenesis (hsa05203 )
Reactome Pathway
Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 )
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 )
HDACs deacetylate histones (R-HSA-3214815 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
NBM-BMX DM5OWXA Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
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14 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID29671355-Compound-13 DMALXYR N. A. N. A. Patented [1]
PMID29671355-Compound-21 DMPJN0M N. A. N. A. Patented [1]
PMID29671355-Compound-23 DMUBOEX N. A. N. A. Patented [1]
PMID29671355-Compound-25 DMPV0KZ N. A. N. A. Patented [1]
PMID29671355-Compound-31 DM3H78D N. A. N. A. Patented [1]
PMID29671355-Compound-36 DMQJ3TC N. A. N. A. Patented [1]
PMID29671355-Compound-37 DMJ1O5R N. A. N. A. Patented [1]
PMID29671355-Compound-43 DMVPMWJ N. A. N. A. Patented [1]
PMID29671355-Compound-44 DM80A3V N. A. N. A. Patented [1]
PMID29671355-Compound-56 DM0VBMI N. A. N. A. Patented [1]
PMID29671355-Compound-61 DMXH1G3 N. A. N. A. Patented [1]
PMID29671355-Compound-62 DMWRS34 N. A. N. A. Patented [1]
PMID29671355-Compound-67 DM1RPL4 N. A. N. A. Patented [1]
PMID29671355-Compound-68b DMLGBR6 N. A. N. A. Patented [1]
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⏷ Show the Full List of 14 Patented Agent(s)
71 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one DM5LSY9 Discovery agent N.A. Investigative [3]
2-(methylsulfonylthio)ethyl 2-propylpentanoate DMM52D3 Discovery agent N.A. Investigative [4]
4-Benzoylamino-N-hydroxy-benzamide DMYBPFS Discovery agent N.A. Investigative [5]
4-Butyrylamino-N-hydroxy-benzamide DMRY6B4 Discovery agent N.A. Investigative [6]
4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide DM5AVG3 Discovery agent N.A. Investigative [7]
4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide DM0M8G5 Discovery agent N.A. Investigative [8]
4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide DMULOHZ Discovery agent N.A. Investigative [7]
4-Phenylbutyrohydroxamic acid DMCZKN7 Discovery agent N.A. Investigative [9]
5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide DM6CRVS Discovery agent N.A. Investigative [10]
5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione DM7KQXL Discovery agent N.A. Investigative [4]
5-Mercapto-pentanoic acid phenylamide DMET3OJ Discovery agent N.A. Investigative [8]
6-(2-Bromo-acetylamino)-hexanoic acid phenylamide DM9LKXD Discovery agent N.A. Investigative [8]
6-(2-mercaptoacetamido)-N-phenylhexanamide DM9P4LB Discovery agent N.A. Investigative [11]
6-benzenesulfinylhexanoic acid hydroxamide DM2I95Z Discovery agent N.A. Investigative [12]
6-benzenesulfonylhexanoic acid hydroxamide DMY9IK8 Discovery agent N.A. Investigative [12]
6-Mercapto-hexanoic acid phenylamide DMD2FW9 Discovery agent N.A. Investigative [8]
6-Phenoxy-hexane-1-thiol DMVYIN2 Discovery agent N.A. Investigative [8]
6-phenylsulfanylhexanoic acid hydroxamide DM3OLM6 Discovery agent N.A. Investigative [12]
7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one DMLCGSY Discovery agent N.A. Investigative [3]
7-(Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one DM28GZ7 Discovery agent N.A. Investigative [13]
7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one DMY027P Discovery agent N.A. Investigative [3]
7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one DM4VQN8 Discovery agent N.A. Investigative [3]
7-Mercapto-heptanoic acid benzothiazol-2-ylamide DMPYTHV Discovery agent N.A. Investigative [8]
7-Mercapto-heptanoic acid biphenyl-3-ylamide DMEQKPO Discovery agent N.A. Investigative [8]
7-Mercapto-heptanoic acid biphenyl-4-ylamide DMJMOUK Discovery agent N.A. Investigative [8]
7-Mercapto-heptanoic acid phenylamide DM4912P Discovery agent N.A. Investigative [8]
7-Mercapto-heptanoic acid pyridin-3-ylamide DMQ9PLA Discovery agent N.A. Investigative [8]
7-Mercapto-heptanoic acid quinolin-3-ylamide DMTAGJ1 Discovery agent N.A. Investigative [8]
8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one DM23XGW Discovery agent N.A. Investigative [3]
8-Mercapto-octanoic acid phenylamide DMD3FWU Discovery agent N.A. Investigative [8]
8-Oxo-8-phenyl-octanoic acid DMXDQ25 Discovery agent N.A. Investigative [7]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide DMVBCID Discovery agent N.A. Investigative [13]
9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one DMIY3D6 Discovery agent N.A. Investigative [13]
9-mercapto-8-oxo-N-phenylnonanamide DMW905K Discovery agent N.A. Investigative [11]
Azithromycin-N-benzyltriazolylhexahydroxamic Acid DM7KD5Y Discovery agent N.A. Investigative [14]
Azithromycin-N-benzyltriazolylnonahydroxamic Acid DMW0HXO Discovery agent N.A. Investigative [14]
Azithromycin-N-benzyltriazolyloctahydroxamic Acid DMAJ4LI Discovery agent N.A. Investigative [14]
Azithromycinarylalkylhydroxamic Acid DM8ZQG3 Discovery agent N.A. Investigative [14]
Cyclostellettamine derivative DMFTDPQ Discovery agent N.A. Investigative [15]
Desclasinose Azithromycinarylalkyl Hydroxamate DMAB9KG Discovery agent N.A. Investigative [14]
droxinostat DM5IA9W Discovery agent N.A. Investigative [16]
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide DM0GOPV Discovery agent N.A. Investigative [17]
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide DMJLFOQ Discovery agent N.A. Investigative [17]
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide DMSUW7M Discovery agent N.A. Investigative [7]
N-(6-Hydroxycarbamoyl-hexyl)-benzamide DMIZVMT Discovery agent N.A. Investigative [7]
N-(6-Mercapto-hexyl)-benzamide DM01Y37 Discovery agent N.A. Investigative [8]
N-hydroxy-1-naphthamide DMZ2T59 Discovery agent N.A. Investigative [18]
N-hydroxy-3-(naphthalen-1-yl)acrylamide DMY6Z0U Discovery agent N.A. Investigative [18]
N-hydroxy-3-phenoxybenzamide DMTZ8RQ Discovery agent N.A. Investigative [18]
N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide DMCN91A Discovery agent N.A. Investigative [5]
N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide DMVK2Y3 Discovery agent N.A. Investigative [5]
N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide DMHEQ41 Discovery agent N.A. Investigative [5]
N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide DMUOCQB Discovery agent N.A. Investigative [5]
N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide DMVEOBY Discovery agent N.A. Investigative [5]
N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide DMISRMT Discovery agent N.A. Investigative [5]
N-hydroxy-4-(naphthalen-1-yl)benzamide DMSHQE3 Discovery agent N.A. Investigative [18]
N-Hydroxy-4-(pentanoylamino-methyl)-benzamide DMGTNQY Discovery agent N.A. Investigative [6]
N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide DMDUOH4 Discovery agent N.A. Investigative [6]
N-Hydroxy-4-phenylacetylamino-benzamide DMCRU17 Discovery agent N.A. Investigative [5]
NILTUBACIN DM0QJSO Discovery agent N.A. Investigative [9]
NMB-T-BMX-OS01 DM5Q9FG Solid tumour/cancer 2A00-2F9Z Investigative [19]
Octanedioic acid bis-hydroxyamide DMJNQ9K Discovery agent N.A. Investigative [9]
Octanedioic acid hydroxyamide pyridin-2-ylamide DMHNWS1 Discovery agent N.A. Investigative [7]
Octanedioic acid hydroxyamide pyridin-4-ylamide DM945RK Discovery agent N.A. Investigative [7]
PCI-34051 DMIMPDL Solid tumour/cancer 2A00-2F9Z Investigative [19]
PSAMMAPLIN A DM6T0IQ Discovery agent N.A. Investigative [13]
S-2,9-dioxo-9-(phenylamino)nonyl ethanethioate DMTH15E Discovery agent N.A. Investigative [11]
ST-2986 DMNERM6 Discovery agent N.A. Investigative [20]
ST-2987 DMWXTM8 Solid tumour/cancer 2A00-2F9Z Investigative [20]
ST-3050 DM19K2D Discovery agent N.A. Investigative [20]
Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester DMBOKSF Discovery agent N.A. Investigative [8]
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⏷ Show the Full List of 71 Investigative Drug(s)

References

1 HDAC inhibitors: a 2013-2017 patent survey.Expert Opin Ther Pat. 2018 Apr 19:1-17.
2 Clinical pipeline report, company report or official report of NatureWise Biotech & Medicals.
3 Heterocyclic ketones as inhibitors of histone deacetylase. Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.
4 New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity. Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7.
5 Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005 Aug 25;48(17):5530-5.
6 Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors. J Med Chem. 2004 Jan 15;47(2):467-74.
7 Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates. J Med Chem. 2002 Feb 14;45(4):753-7.
8 Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxama... J Med Chem. 2005 Feb 24;48(4):1019-32.
9 Chemical phylogenetics of histone deacetylases. Nat Chem Biol. 2010 Mar;6(3):238-243.
10 Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides. Bioorg Med Chem Lett. 2004 May 17;14(10):2477-81.
11 Histone deacetylase inhibitors: from bench to clinic. J Med Chem. 2008 Mar 27;51(6):1505-29.
12 Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides. J Med Chem. 2006 Jan 26;49(2):800-5.
13 Histone deacetylase inhibitors. J Med Chem. 2003 Nov 20;46(24):5097-116.
14 Non-peptide macrocyclic histone deacetylase inhibitors. J Med Chem. 2009 Jan 22;52(2):456-68.
15 Three new cyclostellettamines, which inhibit histone deacetylase, from a marine sponge of the genus Xestospongia. Bioorg Med Chem Lett. 2004 May 17;14(10):2617-20.
16 Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56.
17 Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.
18 Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2874-8.
19 URL: 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).
20 N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC) inhibitors. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9.