Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8O0LF)

• DOT Name: Histone deacetylase 9 (HDAC9)
• Synonyms: HD9; EC 3.5.1.98; Histone deacetylase 7B; HD7; HD7b; Histone deacetylase-related protein; MEF2-interacting transcription repressor MITR
• Gene Name: HDAC9
• UniProt ID: HDAC9_HUMAN
• EC Number: 3.5.1.98
• Pfam ID: PF12203 ; PF00850
• Sequence:
  MHSMISSVDVKSEVPVGLEPISPLDLRTDLRMMMPVVDPVVREKQLQQELLLIQQQQQIQ
  KQLLIAEFQKQHENLTRQHQAQLQEHIKELLAIKQQQELLEKEQKLEQQRQEQEVERHRR
  EQQLPPLRGKDRGRERAVASTEVKQKLQEFLLSKSATKDTPTNGKNHSVSRHPKLWYTAA
  HHTSLDQSSPPLSGTSPSYKYTLPGAQDAKDDFPLRKTASEPNLKVRSRLKQKVAERRSS
  PLLRRKDGNVVTSFKKRMFEVTESSVSSSSPGSGPSSPNNGPTGSVTENETSVLPPTPHA
  EQMVSQQRILIHEDSMNLLSLYTSPSLPNITLGLPAVPSQLNASNSLKEKQKCETQTLRQ
  GVPLPGQYGGSIPASSSHPHVTLEGKPPNSSHQALLQHLLLKEQMRQQKLLVAGGVPLHP
  QSPLATKERISPGIRGTHKLPRHRPLNRTQSAPLPQSTLAQLVIQQQHQQFLEKQKQYQQ
  QIHMNKLLSKSIEQLKQPGSHLEEAEEELQGDQAMQEDRAPSSGNSTRSDSSACVDDTLG
  QVGAVKVKEEPVDSDEDAQIQEMESGEQAAFMQQPFLEPTHTRALSVRQAPLAAVGMDGL
  EKHRLVSRTHSSPAASVLPHPAMDRPLQPGSATGIAYDPLMLKHQCVCGNSTTHPEHAGR
  IQSIWSRLQETGLLNKCERIQGRKASLEEIQLVHSEHHSLLYGTNPLDGQKLDPRILLGD
  DSQKFFSSLPCGGLGVDSDTIWNELHSSGAARMAVGCVIELASKVASGELKNGFAVVRPP
  GHHAEESTAMGFCFFNSVAITAKYLRDQLNISKILIVDLDVHHGNGTQQAFYADPSILYI
  SLHRYDEGNFFPGSGAPNEVGTGLGEGYNINIAWTGGLDPPMGDVEYLEAFRTIVKPVAK
  EFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTA
  ICDASEACVNALLGNELEPLAEDILHQSPNMNAVISLQKIIEIQSMSLKFS
• 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. Represses MEF2-dependent transcription; Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.
• Tissue Specificity: Broadly expressed, with highest levels in brain, heart, muscle and testis. Isoform 3 is present in human bladder carcinoma cells (at protein level).
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  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)
  Notch-HLH transcription pathway (R-HSA-350054)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Histone deacetylase 9 (HDAC9) increases the response to substance of Paclitaxel.	[26]
Mitomycin	DMH0ZJE	Approved	Histone deacetylase 9 (HDAC9) affects the response to substance of Mitomycin.	[27]
Topotecan	DMP6G8T	Approved	Histone deacetylase 9 (HDAC9) affects the response to substance of Topotecan.	[27]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histone deacetylase 9 (HDAC9).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Histone deacetylase 9 (HDAC9).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Histone deacetylase 9 (HDAC9).	[20]

25 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone deacetylase 9 (HDAC9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone deacetylase 9 (HDAC9).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone deacetylase 9 (HDAC9).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone deacetylase 9 (HDAC9).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Histone deacetylase 9 (HDAC9).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Histone deacetylase 9 (HDAC9).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone deacetylase 9 (HDAC9).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Histone deacetylase 9 (HDAC9).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Histone deacetylase 9 (HDAC9).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Histone deacetylase 9 (HDAC9).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Histone deacetylase 9 (HDAC9).	[13]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Histone deacetylase 9 (HDAC9).	[9]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Histone deacetylase 9 (HDAC9).	[14]
Pirfenidone	DM6VZFQ	Approved	Pirfenidone decreases the expression of Histone deacetylase 9 (HDAC9).	[10]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone deacetylase 9 (HDAC9).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone deacetylase 9 (HDAC9).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Histone deacetylase 9 (HDAC9).	[10]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Histone deacetylase 9 (HDAC9).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone deacetylase 9 (HDAC9).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone deacetylase 9 (HDAC9).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone deacetylase 9 (HDAC9).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone deacetylase 9 (HDAC9).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone deacetylase 9 (HDAC9).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Histone deacetylase 9 (HDAC9).	[24]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Histone deacetylase 9 (HDAC9).	[25]

References

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• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
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• [23] Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 2012 Sep 15;21(18):4104-14. doi: 10.1093/hmg/dds239. Epub 2012 Jun 20.
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