Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTQGH8)

• DTT Name: Histone deacetylase 4 (HDAC4)
• Synonyms: KIAA0288; HD4
• Gene Name: HDAC4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Carbon-nitrogen hydrolase
• UniProt ID: HDAC4_HUMAN
• TTD ID: T63816
• EC Number: EC 3.5.1.98
• Sequence:
  MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLP
  VAEPALREQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLA
  MKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVL
  NKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFP
  LRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGP
  SSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPA
  TGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLL
  EQPPAQAPLVTGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQNAQALQHL
  VIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPY
  LDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQ
  RIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRFTTGLVYDT
  LMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHT
  LLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVE
  LVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWD
  VHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDP
  PMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQL
  MGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKV
  MEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEE
  EPPL
• 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).
• KEGG Pathway:
  Alcoholism (hsa05034)
  Epstein-Barr virus infection (hsa05169)
  Viral carcinogenesis (hsa05203)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)

Molecular Interaction Atlas (MIA) of This DTT

23 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID29671355-Compound-12	DMBQOW4	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-21	DMPJN0M	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-23	DMUBOEX	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-25	DMPV0KZ	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-31	DM3H78D	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-43	DMVPMWJ	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-45a	DM5LYKR	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-47a	DM5I1QV	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-47b	DMBUJ39	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-47c	DMAH982	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-47d	DMPA9OY	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-50	DMLDFVN	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-52	DMEUZM3	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-56	DM0VBMI	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-61	DMXH1G3	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-62	DMWRS34	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-67	DM1RPL4	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-68b	DMLGBR6	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-70	DM394WH	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-71a	DMUAC1T	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-71b	DM8VG4Q	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-72a	DMICDV6	N. A.	N. A.	Patented	[2]
PMID29671355-Compound-72b	DM08OV7	N. A.	N. A.	Patented	[2]

81 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]
2,2-bis(3-fluorophenyl)-N-hydroxyacetamide	DMTODR2	Discovery agent	N.A.	Investigative	[4]
2,2-bis(4-chlorophenyl)-N-hydroxyacetamide	DM2RKD6	Discovery agent	N.A.	Investigative	[4]
2,2-bis(4-fluorophenyl)-N-hydroxyacetamide	DM5PWQM	Discovery agent	N.A.	Investigative	[4]
2-(methylsulfonylthio)ethyl 2-propylpentanoate	DMM52D3	Discovery agent	N.A.	Investigative	[5]
4-Benzoylamino-N-hydroxy-benzamide	DMYBPFS	Discovery agent	N.A.	Investigative	[6]
4-Butyrylamino-N-hydroxy-benzamide	DMRY6B4	Discovery agent	N.A.	Investigative	[7]
4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide	DM5AVG3	Discovery agent	N.A.	Investigative	[8]
4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide	DM0M8G5	Discovery agent	N.A.	Investigative	[9]
4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide	DMULOHZ	Discovery agent	N.A.	Investigative	[10]
5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide	DM6CRVS	Discovery agent	N.A.	Investigative	[11]
5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione	DM7KQXL	Discovery agent	N.A.	Investigative	[5]
5-Mercapto-pentanoic acid phenylamide	DMET3OJ	Discovery agent	N.A.	Investigative	[9]
6-(2-Bromo-acetylamino)-hexanoic acid phenylamide	DM9LKXD	Discovery agent	N.A.	Investigative	[9]
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	[9]
6-Phenoxy-hexane-1-thiol	DMVYIN2	Discovery agent	N.A.	Investigative	[9]
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	[8]
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	[9]
7-Mercapto-heptanoic acid biphenyl-3-ylamide	DMEQKPO	Discovery agent	N.A.	Investigative	[9]
7-Mercapto-heptanoic acid biphenyl-4-ylamide	DMJMOUK	Discovery agent	N.A.	Investigative	[9]
7-Mercapto-heptanoic acid phenylamide	DM4912P	Discovery agent	N.A.	Investigative	[9]
7-Mercapto-heptanoic acid pyridin-3-ylamide	DMQ9PLA	Discovery agent	N.A.	Investigative	[9]
7-Mercapto-heptanoic acid quinolin-3-ylamide	DMTAGJ1	Discovery agent	N.A.	Investigative	[9]
7-mercapto-N-(4-phenylthiazol-2-yl)heptanamide	DM03XYF	Discovery agent	N.A.	Investigative	[13]
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	[9]
8-Oxo-8-phenyl-octanoic acid	DMXDQ25	Discovery agent	N.A.	Investigative	[10]
8-Oxo-8-phenyl-octanoic acid hydroxyamide	DMWM1UL	Discovery agent	N.A.	Investigative	[8]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide	DMVBCID	Discovery agent	N.A.	Investigative	[8]
9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one	DMIY3D6	Discovery agent	N.A.	Investigative	[8]
AZUMAMIDE B	DMXOGE8	Discovery agent	N.A.	Investigative	[14]
AZUMAMIDE C	DMEBA61	Discovery agent	N.A.	Investigative	[14]
AZUMAMIDE E	DMAX06G	Discovery agent	N.A.	Investigative	[14]
Cyclo(-L-Am7(S2Py)-A2in-L-Ala-D-Pro-)	DMZF35W	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Pro-)	DMIVREK	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Tic-)	DMLBECR	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ph4-D-Pro-)	DMA76KW	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ph5-D-Pro-)	DMLNJ0O	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Phe-D-Pro-)	DMTVMWA	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Phg-D-Pro-)	DMUSEDF	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ser(Bzl)-D-Pro-)	DMSEQ0W	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-Aib-L-Ser-D-Pro-)	DMBKP48	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-D-2MePhe-L-Ala-D-Pro-)	DMVY89X	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-D-A1in-L-Ala-D-Pro-)	DMTDIM9	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-L-2MePhe-L-Ala-D-Pro-)	DMV23XD	Discovery agent	N.A.	Investigative	[15]
Cyclo(-L-Am7(S2Py)-L-A1in-L-Ala-D-Pro-)	DM0VIH4	Discovery agent	N.A.	Investigative	[15]
Cyclostellettamine derivative	DMFTDPQ	Discovery agent	N.A.	Investigative	[16]
LARGAZOLE	DMSYLIJ	Discovery agent	N.A.	Investigative	[17]
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide	DM0GOPV	Discovery agent	N.A.	Investigative	[18]
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide	DMJLFOQ	Discovery agent	N.A.	Investigative	[18]
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide	DMSUW7M	Discovery agent	N.A.	Investigative	[8]
N-(6-Hydroxycarbamoyl-hexyl)-benzamide	DMIZVMT	Discovery agent	N.A.	Investigative	[10]
N-(6-Mercapto-hexyl)-benzamide	DM01Y37	Discovery agent	N.A.	Investigative	[9]
N-hydroxy-2,2-diphenylacetamide	DMX3KRQ	Discovery agent	N.A.	Investigative	[4]
N-hydroxy-2,2-diphenylpropanamide	DM7I2TD	Discovery agent	N.A.	Investigative	[4]
N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide	DMCN91A	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide	DMVK2Y3	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide	DMHEQ41	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide	DMUOCQB	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide	DMVEOBY	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide	DMISRMT	Discovery agent	N.A.	Investigative	[6]
N-Hydroxy-4-(pentanoylamino-methyl)-benzamide	DMGTNQY	Discovery agent	N.A.	Investigative	[7]
N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide	DMDUOH4	Discovery agent	N.A.	Investigative	[7]
N-Hydroxy-4-phenylacetylamino-benzamide	DMCRU17	Discovery agent	N.A.	Investigative	[6]
N-hydroxy-9,10-dihydroanthracene-9-carboxamide	DMID3BF	Discovery agent	N.A.	Investigative	[4]
N-hydroxy-9H-xanthene-9-carboxamide	DM0DRHP	Discovery agent	N.A.	Investigative	[4]
Octanedioic acid bis-hydroxyamide	DMJNQ9K	Discovery agent	N.A.	Investigative	[19]
Octanedioic acid hydroxyamide pyridin-2-ylamide	DMHNWS1	Discovery agent	N.A.	Investigative	[10]
Octanedioic acid hydroxyamide pyridin-4-ylamide	DM945RK	Discovery agent	N.A.	Investigative	[10]
PSAMMAPLIN A	DM6T0IQ	Discovery agent	N.A.	Investigative	[8]
santacruzamate A	DMFAM7P	Discovery agent	N.A.	Investigative	[20]
ST-2987	DMWXTM8	Solid tumour/cancer	2A00-2F9Z	Investigative	[21]
ST-3050	DM19K2D	Discovery agent	N.A.	Investigative	[21]
Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester	DMBOKSF	Discovery agent	N.A.	Investigative	[9]
TMP269	DMSMQE7	Discovery agent	N.A.	Investigative	[22]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	3.51E-03	1.95	1.48
Renal cancer	2C82	Kidney	6.31E-01	-0.12	-0.17

References

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• [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] 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.
• [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.
• [15] Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework. Bioorg Med Chem. 2007 Dec 15;15(24):7830-9.
• [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.
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• [18] Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.
• [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.
• [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.
• [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.
• [22] Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013 May;9(5):319-25.