Target Information
| Target General Information | Top | |||||
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| Target ID |
T63816
(Former ID: TTDC00159)
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| Target Name |
Histone deacetylase 4 (HDAC4)
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| Synonyms |
KIAA0288; HD4
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| Gene Name |
HDAC4
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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. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1. 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 |
MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLP
VAEPALREQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLA MKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVL NKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFP LRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGP SSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPA TGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLL EQPPAQAPLVTGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQNAQALQHL VIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPY LDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQ RIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRFTTGLVYDT LMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHT LLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVE LVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWD VHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDP PMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQL MGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKV MEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEE EPPL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T63T5P | |||||
| 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 | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| 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-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Wikipedia: Quisinostat | |||||
| REF 2 | HDAC inhibitors: a 2013-2017 patent survey.Expert Opin Ther Pat. 2018 Apr 19:1-17. | |||||
| REF 3 | Heterocyclic ketones as inhibitors of histone deacetylase. Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13. | |||||
| REF 4 | Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. | |||||
| 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 | Histone deacetylase inhibitors. J Med Chem. 2003 Nov 20;46(24):5097-116. | |||||
| 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 | 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 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 | 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 13 | Design, synthesis, structure--selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhib... J Med Chem. 2007 Nov 1;50(22):5425-38. | |||||
| REF 14 | Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells. Bioorg Med Chem Lett. 2008 May 1;18(9):2982-4. | |||||
| REF 15 | Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework. Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. | |||||
| 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 | Synthesis and biological characterization of the histone deacetylase inhibitor largazole and C7- modified analogues. J Med Chem. 2010 Jun 24;53(12):4654-67. | |||||
| REF 18 | Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72. | |||||
| REF 19 | Structure-activity relationships on phenylalanine-containing inhibitors of histone deacetylase: in vitro enzyme inhibition, induction of differenti... J Med Chem. 2002 Jul 18;45(15):3296-309. | |||||
| REF 20 | 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 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. | |||||
| REF 22 | Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013 May;9(5):319-25. | |||||
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