Target Information
| Target General Information | Top | |||||
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| Target ID |
T28887
(Former ID: TTDR01337)
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| Target Name |
Histone deacetylase 8 (HDAC8)
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| Synonyms |
Histone deacetylase-8; HDACL1; HD8; CDA07
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| Gene Name |
HDAC8
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 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).
Click to Show/Hide
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| BioChemical Class |
Carbon-nitrogen hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.5.1.98
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| Sequence |
MEEPEEPADSGQSLVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPK
VASMEEMATFHTDAYLQHLQKVSQEGDDDHPDSIEYGLGYDCPATEGIFDYAAAIGGATI TAAQCLIDGMCKVAINWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLH HGDGVEDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGIQDEKY YQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIGKCLKYILQWQLATLI LGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEFFTAYGPDYVLEITPSCRPDRNEPH RIQQILNYIKGNLKHVV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T90RVD | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | NBM-BMX | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 86 Inhibitor drugs | + | ||||
| 1 | NBM-BMX | Drug Info | [3] | |||
| 2 | PMID29671355-Compound-13 | Drug Info | [1] | |||
| 3 | PMID29671355-Compound-21 | Drug Info | [1] | |||
| 4 | PMID29671355-Compound-23 | Drug Info | [1] | |||
| 5 | PMID29671355-Compound-25 | Drug Info | [1] | |||
| 6 | PMID29671355-Compound-31 | Drug Info | [1] | |||
| 7 | PMID29671355-Compound-36 | Drug Info | [1] | |||
| 8 | PMID29671355-Compound-37 | Drug Info | [1] | |||
| 9 | PMID29671355-Compound-43 | Drug Info | [1] | |||
| 10 | PMID29671355-Compound-44 | Drug Info | [1] | |||
| 11 | PMID29671355-Compound-56 | Drug Info | [1] | |||
| 12 | PMID29671355-Compound-61 | Drug Info | [1] | |||
| 13 | PMID29671355-Compound-62 | Drug Info | [1] | |||
| 14 | PMID29671355-Compound-67 | Drug Info | [1] | |||
| 15 | PMID29671355-Compound-68b | Drug Info | [1] | |||
| 16 | (E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one | Drug Info | [4] | |||
| 17 | 2-(methylsulfonylthio)ethyl 2-propylpentanoate | Drug Info | [5] | |||
| 18 | 4-Benzoylamino-N-hydroxy-benzamide | Drug Info | [6] | |||
| 19 | 4-Butyrylamino-N-hydroxy-benzamide | Drug Info | [7] | |||
| 20 | 4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide | Drug Info | [8] | |||
| 21 | 4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide | Drug Info | [9] | |||
| 22 | 4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide | Drug Info | [8] | |||
| 23 | 4-Phenylbutyrohydroxamic acid | Drug Info | [10] | |||
| 24 | 5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide | Drug Info | [11] | |||
| 25 | 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione | Drug Info | [5] | |||
| 26 | 5-Mercapto-pentanoic acid phenylamide | Drug Info | [9] | |||
| 27 | 6-(2-Bromo-acetylamino)-hexanoic acid phenylamide | Drug Info | [9] | |||
| 28 | 6-(2-mercaptoacetamido)-N-phenylhexanamide | Drug Info | [12] | |||
| 29 | 6-benzenesulfinylhexanoic acid hydroxamide | Drug Info | [13] | |||
| 30 | 6-benzenesulfonylhexanoic acid hydroxamide | Drug Info | [13] | |||
| 31 | 6-Mercapto-hexanoic acid phenylamide | Drug Info | [9] | |||
| 32 | 6-Phenoxy-hexane-1-thiol | Drug Info | [9] | |||
| 33 | 6-phenylsulfanylhexanoic acid hydroxamide | Drug Info | [13] | |||
| 34 | 7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one | Drug Info | [4] | |||
| 35 | 7-(Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one | Drug Info | [14] | |||
| 36 | 7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one | Drug Info | [4] | |||
| 37 | 7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one | Drug Info | [4] | |||
| 38 | 7-Mercapto-heptanoic acid benzothiazol-2-ylamide | Drug Info | [9] | |||
| 39 | 7-Mercapto-heptanoic acid biphenyl-3-ylamide | Drug Info | [9] | |||
| 40 | 7-Mercapto-heptanoic acid biphenyl-4-ylamide | Drug Info | [9] | |||
| 41 | 7-Mercapto-heptanoic acid phenylamide | Drug Info | [9] | |||
| 42 | 7-Mercapto-heptanoic acid pyridin-3-ylamide | Drug Info | [9] | |||
| 43 | 7-Mercapto-heptanoic acid quinolin-3-ylamide | Drug Info | [9] | |||
| 44 | 8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one | Drug Info | [4] | |||
| 45 | 8-Mercapto-octanoic acid phenylamide | Drug Info | [9] | |||
| 46 | 8-Oxo-8-phenyl-octanoic acid | Drug Info | [8] | |||
| 47 | 9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide | Drug Info | [14] | |||
| 48 | 9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one | Drug Info | [14] | |||
| 49 | 9-mercapto-8-oxo-N-phenylnonanamide | Drug Info | [12] | |||
| 50 | Azithromycin-N-benzyltriazolylhexahydroxamic Acid | Drug Info | [15] | |||
| 51 | Azithromycin-N-benzyltriazolylnonahydroxamic Acid | Drug Info | [15] | |||
| 52 | Azithromycin-N-benzyltriazolyloctahydroxamic Acid | Drug Info | [15] | |||
| 53 | Azithromycinarylalkylhydroxamic Acid | Drug Info | [15] | |||
| 54 | Cyclostellettamine derivative | Drug Info | [16] | |||
| 55 | Desclasinose Azithromycinarylalkyl Hydroxamate | Drug Info | [15] | |||
| 56 | droxinostat | Drug Info | [17] | |||
| 57 | N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide | Drug Info | [18] | |||
| 58 | N-(2-Mercapto-ethyl)-N'-phenyl-succinamide | Drug Info | [18] | |||
| 59 | N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide | Drug Info | [8] | |||
| 60 | N-(6-Hydroxycarbamoyl-hexyl)-benzamide | Drug Info | [8] | |||
| 61 | N-(6-Mercapto-hexyl)-benzamide | Drug Info | [9] | |||
| 62 | N-hydroxy-1-naphthamide | Drug Info | [19] | |||
| 63 | N-hydroxy-3-(naphthalen-1-yl)acrylamide | Drug Info | [19] | |||
| 64 | N-hydroxy-3-phenoxybenzamide | Drug Info | [19] | |||
| 65 | N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide | Drug Info | [6] | |||
| 66 | N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide | Drug Info | [6] | |||
| 67 | N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide | Drug Info | [6] | |||
| 68 | N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide | Drug Info | [6] | |||
| 69 | N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide | Drug Info | [6] | |||
| 70 | N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide | Drug Info | [6] | |||
| 71 | N-hydroxy-4-(naphthalen-1-yl)benzamide | Drug Info | [19] | |||
| 72 | N-Hydroxy-4-(pentanoylamino-methyl)-benzamide | Drug Info | [7] | |||
| 73 | N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide | Drug Info | [7] | |||
| 74 | N-Hydroxy-4-phenylacetylamino-benzamide | Drug Info | [6] | |||
| 75 | NILTUBACIN | Drug Info | [10] | |||
| 76 | NMB-T-BMX-OS01 | Drug Info | [20] | |||
| 77 | Octanedioic acid bis-hydroxyamide | Drug Info | [10] | |||
| 78 | Octanedioic acid hydroxyamide pyridin-2-ylamide | Drug Info | [8] | |||
| 79 | Octanedioic acid hydroxyamide pyridin-4-ylamide | Drug Info | [8] | |||
| 80 | PCI-34051 | Drug Info | [20] | |||
| 81 | PSAMMAPLIN A | Drug Info | [14] | |||
| 82 | S-2,9-dioxo-9-(phenylamino)nonyl ethanethioate | Drug Info | [12] | |||
| 83 | ST-2986 | Drug Info | [21] | |||
| 84 | ST-2987 | Drug Info | [21] | |||
| 85 | ST-3050 | Drug Info | [21] | |||
| 86 | Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester | Drug Info | [9] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Alcoholism | |||||
| 2 | Viral carcinogenesis | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Wnt signaling pathway | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Signaling events mediated by HDAC Class I | |||||
| Reactome | [+] 4 Reactome Pathways | + | ||||
| 1 | NOTCH1 Intracellular Domain Regulates Transcription | |||||
| 2 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | |||||
| 3 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | |||||
| 4 | HDACs deacetylate histones | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Integrated Pancreatic Cancer Pathway | |||||
| 2 | Neural Crest Differentiation | |||||
| 3 | Cell Cycle | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | HDAC inhibitors: a 2013-2017 patent survey.Expert Opin Ther Pat. 2018 Apr 19:1-17. | |||||
| REF 2 | ClinicalTrials.gov (NCT03808870) A Safety and Pharmacokinetic Study of NBM-BMX Administered Orally to Asian Patients With Advanced Cancer. U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of NatureWise Biotech & Medicals. | |||||
| REF 4 | Heterocyclic ketones as inhibitors of histone deacetylase. Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13. | |||||
| REF 5 | New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity. Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7. | |||||
| REF 6 | Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005 Aug 25;48(17):5530-5. | |||||
| REF 7 | 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. | |||||
| REF 8 | 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. | |||||
| REF 9 | 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. | |||||
| REF 10 | Chemical phylogenetics of histone deacetylases. Nat Chem Biol. 2010 Mar;6(3):238-243. | |||||
| REF 11 | 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. | |||||
| REF 12 | Histone deacetylase inhibitors: from bench to clinic. J Med Chem. 2008 Mar 27;51(6):1505-29. | |||||
| REF 13 | Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides. J Med Chem. 2006 Jan 26;49(2):800-5. | |||||
| REF 14 | Histone deacetylase inhibitors. J Med Chem. 2003 Nov 20;46(24):5097-116. | |||||
| REF 15 | Non-peptide macrocyclic histone deacetylase inhibitors. J Med Chem. 2009 Jan 22;52(2):456-68. | |||||
| REF 16 | 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. | |||||
| REF 17 | Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56. | |||||
| REF 18 | Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72. | |||||
| REF 19 | Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2874-8. | |||||
| REF 20 | 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). | |||||
| REF 21 | 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. | |||||
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