Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4QEH6T)

• DOT Name: Transducin-like enhancer protein 4 (TLE4)
• Synonyms: Grg-4; Groucho-related protein 4
• Gene Name: TLE4
• Related Disease:
  Lung cancer
  Lung carcinoma
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adenoma
  Breast cancer
  Breast carcinoma
  Chromosomal disorder
  Colorectal carcinoma
  Epilepsy
  Myeloid leukaemia
  Myocardial ischemia
  Bipolar disorder
  Adult lymphoma
  Asthma
  Carcinoma
  Lymphoma
  Neoplasm
  Pediatric lymphoma
  Undifferentiated carcinoma
• UniProt ID: TLE4_HUMAN
• Pfam ID: PF03920 ; PF00400
• Sequence:
  MIRDLSKMYPQTRHPAPHQPAQPFKFTISESCDRIKEEFQFLQAQYHSLKLECEKLASEK
  TEMQRHYVMYYEMSYGLNIEMHKQAEIVKRLNAICAQVIPFLSQEHQQQVVQAVERAKQV
  TMAELNAIIGQQLQAQHLSHGHGLPVPLTPHPSGLQPPAIPPIGSSAGLLALSSALGGQS
  HLPIKDEKKHHDNDHQRDRDSIKSSSVSPSASFRGAEKHRNSADYSSESKKQKTEEKEIA
  ARYDSDGEKSDDNLVVDVSNEDPSSPRGSPAHSPRENGLDKTRLLKKDAPISPASIASSS
  STPSSKSKELSLNEKSTTPVSKSNTPTPRTDAPTPGSNSTPGLRPVPGKPPGVDPLASSL
  RTPMAVPCPYPTPFGIVPHAGMNGELTSPGAAYAGLHNISPQMSAAAAAAAAAAAYGRSP
  VVGFDPHHHMRVPAIPPNLTGIPGGKPAYSFHVSADGQMQPVPFPPDALIGPGIPRHARQ
  INTLNHGEVVCAVTISNPTRHVYTGGKGCVKVWDISHPGNKSPVSQLDCLNRDNYIRSCR
  LLPDGRTLIVGGEASTLSIWDLAAPTPRIKAELTSSAPACYALAISPDSKVCFSCCSDGN
  IAVWDLHNQTLVRQFQGHTDGASCIDISNDGTKLWTGGLDNTVRSWDLREGRQLQQHDFT
  SQIFSLGYCPTGEWLAVGMENSNVEVLHVTKPDKYQLHLHESCVLSLKFAHCGKWFVSTG
  KDNLLNAWRTPYGASIFQSKESSSVLSCDISVDDKYIVTGSGDKKATVYEVIY
• Function: Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression. Involved in transcriptional repression of GNRHR and enhances MSX1-mediated transcriptional repression of CGA/alpha-GSU.
• Tissue Specificity: In all tissues examined, mostly in brain, and muscle.
• KEGG Pathway:
  Wnt sig.ling pathway (hsa04310)
  Notch sig.ling pathway (hsa04330)
• Reactome Pathway:
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Repression of WNT target genes (R-HSA-4641265)
  Formation of the beta-catenin (R-HSA-201722)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Adenoma	DIS78ZEV	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Epilepsy	DISBB28L	Strong	Biomarker	[8]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[9]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[10]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[11]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[12]
Asthma	DISW9QNS	Limited	Biomarker	[13]
Carcinoma	DISH9F1N	Limited	Biomarker	[14]
Lymphoma	DISN6V4S	Limited	Altered Expression	[12]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[12]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[14]

22 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 Transducin-like enhancer protein 4 (TLE4).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transducin-like enhancer protein 4 (TLE4).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Transducin-like enhancer protein 4 (TLE4).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[19]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Transducin-like enhancer protein 4 (TLE4).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transducin-like enhancer protein 4 (TLE4).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transducin-like enhancer protein 4 (TLE4).	[23]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[24]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[25]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transducin-like enhancer protein 4 (TLE4).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[24]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Transducin-like enhancer protein 4 (TLE4).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transducin-like enhancer protein 4 (TLE4).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transducin-like enhancer protein 4 (TLE4).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[31]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Transducin-like enhancer protein 4 (TLE4).	[32]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transducin-like enhancer protein 4 (TLE4).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transducin-like enhancer protein 4 (TLE4).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transducin-like enhancer protein 4 (TLE4).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transducin-like enhancer protein 4 (TLE4).	[34]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transducin-like enhancer protein 4 (TLE4).	[37]

References

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