Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc finger E-box-binding homeobox 1
• Synonyms: NIL-2-A zinc finger protein; Negative regulator of IL2; Transcription factor 8; TCF-8
• Gene Name: ZEB1
• Related Disease:
  Posterior polymorphous corneal dystrophy 3
  Fuchs' endothelial dystrophy
  Posterior polymorphous corneal dystrophy
  Corneal dystrophy, Fuchs endothelial, 6
• UniProt ID: ZEB1_HUMAN
• PDB ID: 2.00E+19
• Pfam ID: PF00096 ; PF05605
• Sequence:
  MADGPRCKRRKQANPRRNNVTNYNTVVETNSDSDDEDKLHIVEEESVTDAADCEGVPEDD
  LPTDQTVLPGRSSEREGNAKNCWEDDRKEGQEILGPEAQADEAGCTVKDDECESDAENEQ
  NHDPNVEEFLQQQDTAVIFPEAPEEDQRQGTPEASGHDENGTPDAFSQLLTCPYCDRGYK
  RFTSLKEHIKYRHEKNEDNFSCSLCSYTFAYRTQLERHMTSHKSGRDQRHVTQSGCNRKF
  KCTECGKAFKYKHHLKEHLRIHSGEKPYECPNCKKRFSHSGSYSSHISSKKCISLIPVNG
  RPRTGLKTSQCSSPSLSASPGSPTRPQIRQKIENKPLQEQLSVNQIKTEPVDYEFKPIVV
  ASGINCSTPLQNGVFTGGGPLQATSSPQGMVQAVVLPTVGLVSPISINLSDIQNVLKVAV
  DGNVIRQVLENNQANLASKEQETINASPIQQGGHSVISAISLPLVDQDGTTKIIINYSLE
  QPSQLQVVPQNLKKENPVATNSCKSEKLPEDLTVKSEKDKSFEGGVNDSTCLLCDDCPGD
  INALPELKHYDLKQPTQPPPLPAAEAEKPESSVSSATGDGNLSPSQPPLKNLLSLLKAYY
  ALNAQPSAEELSKIADSVNLPLDVVKKWFEKMQAGQISVQSSEPSSPEPGKVNIPAKNND
  QPQSANANEPQDSTVNLQSPLKMTNSPVLPVGSTTNGSRSSTPSPSPLNLSSSRNTQGYL
  YTAEGAQEEPQVEPLDLSLPKQQGELLERSTITSVYQNSVYSVQEEPLNLSCAKKEPQKD
  SCVTDSEPVVNVIPPSANPINIAIPTVTAQLPTIVAIADQNSVPCLRALAANKQTILIPQ
  VAYTYSTTVSPAVQEPPLKVIQPNGNQDERQDTSSEGVSNVEDQNDSDSTPPKKKMRKTE
  NGMYACDLCDKIFQKSSSLLRHKYEHTGKRPHECGICKKAFKHKHHLIEHMRLHSGEKPY
  QCDKCGKRFSHSGSYSQHMNHRYSYCKREAEERDSTEQEEAGPEILSNEHVGARASPSQG
  DSDERESLTREEDEDSEKEEEEEDKEMEELQEEKECEKPQGDEEEEEEEEEVEEEEVEEA
  ENEGEEAKTEGLMKDDRAESQASSLGQKVGESSEQVSEEKTNEA
• Function: Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region.
• Tissue Specificity: Colocalizes with SMARCA4/BRG1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level). Expressed in heart and skeletal muscle, but not in liver, spleen, or pancreas.
• KEGG Pathway:
  Transcriptio.l misregulation in cancer (hsa05202)
  MicroR.s in cancer (hsa05206)
  Prostate cancer (hsa05215)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Posterior polymorphous corneal dystrophy 3	DISZY75E	Definitive	Autosomal dominant	[1]
Fuchs' endothelial dystrophy	DISL7TXC	Supportive	Autosomal dominant	[2]
Posterior polymorphous corneal dystrophy	DISHAYH6	Supportive	Autosomal dominant	[3]
Corneal dystrophy, Fuchs endothelial, 6	DISVK3ZA	Limited	Autosomal dominant	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Zinc finger E-box-binding homeobox 1 affects the response to substance of Topotecan.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Zinc finger E-box-binding homeobox 1.	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Zinc finger E-box-binding homeobox 1.	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger E-box-binding homeobox 1.	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Zinc finger E-box-binding homeobox 1.	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger E-box-binding homeobox 1.	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger E-box-binding homeobox 1.	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Zinc finger E-box-binding homeobox 1.	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Zinc finger E-box-binding homeobox 1.	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Zinc finger E-box-binding homeobox 1.	[14]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Zinc finger E-box-binding homeobox 1.	[15]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Zinc finger E-box-binding homeobox 1.	[16]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Zinc finger E-box-binding homeobox 1.	[17]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Zinc finger E-box-binding homeobox 1.	[18]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Zinc finger E-box-binding homeobox 1.	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Zinc finger E-box-binding homeobox 1.	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Zinc finger E-box-binding homeobox 1.	[21]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Zinc finger E-box-binding homeobox 1.	[22]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Zinc finger E-box-binding homeobox 1.	[23]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Zinc finger E-box-binding homeobox 1.	[24]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Zinc finger E-box-binding homeobox 1.	[25]
Warfarin	DMJYCVW	Approved	Warfarin decreases the expression of Zinc finger E-box-binding homeobox 1.	[26]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Zinc finger E-box-binding homeobox 1.	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Zinc finger E-box-binding homeobox 1.	[27]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Zinc finger E-box-binding homeobox 1.	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Zinc finger E-box-binding homeobox 1.	[16]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Zinc finger E-box-binding homeobox 1.	[11]
AMG 232	DM65PTO	Phase 2	AMG 232 decreases the expression of Zinc finger E-box-binding homeobox 1.	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc finger E-box-binding homeobox 1.	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Zinc finger E-box-binding homeobox 1.	[31]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Zinc finger E-box-binding homeobox 1.	[33]
EMBELIN	DMFZO4Y	Terminated	EMBELIN decreases the expression of Zinc finger E-box-binding homeobox 1.	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Zinc finger E-box-binding homeobox 1.	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger E-box-binding homeobox 1.	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the expression of Zinc finger E-box-binding homeobox 1.	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Zinc finger E-box-binding homeobox 1.	[39]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Zinc finger E-box-binding homeobox 1.	[40]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Zinc finger E-box-binding homeobox 1.	[28]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Zinc finger E-box-binding homeobox 1.	[41]
NADA	DM3ORGM	Investigative	NADA decreases the expression of Zinc finger E-box-binding homeobox 1.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Zinc finger E-box-binding homeobox 1.	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Zinc finger E-box-binding homeobox 1.	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc finger E-box-binding homeobox 1.	[34]

References

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