Details of Drug Off-Target (DOT)

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

• DOT Name: COUP transcription factor 1 (NR2F1)
• Synonyms: COUP-TF1; COUP transcription factor I; COUP-TF I; Nuclear receptor subfamily 2 group F member 1; V-erbA-related protein 3; EAR-3
• Gene Name: NR2F1
• Related Disease:
  Anxiety
  Anxiety disorder
  Bosch-Boonstra-Schaaf optic atrophy syndrome
  Adenoma
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Congenital diaphragmatic hernia
  Endometrial cancer
  Endometrial carcinoma
  Esophageal squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Intellectual disability
  Osteosarcoma
  Thyroid gland carcinoma
  West syndrome
  Neoplasm
  Bladder transitional cell carcinoma
  Tarsal-carpal coalition syndrome
  Breast neoplasm
  Rheumatoid arthritis
• UniProt ID: COT1_HUMAN
• PDB ID: 2EBL
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MAMVVSSWRDPQDDVAGGNPGGPNPAAQAARGGGGGAGEQQQQAGSGAPHTPQTPGQPGA
  PATPGTAGDKGQGPPGSGQSQQHIECVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTY
  TCRANRNCPIDQHHRNQCQYCRLKKCLKVGMRREAVQRGRMPPTQPNPGQYALTNGDPLN
  GHCYLSGYISLLLRAEPYPTSRYGSQCMQPNNIMGIENICELAARLLFSAVEWARNIPFF
  PDLQITDQVSLLRLTWSELFVLNAAQCSMPLHVAPLLAAAGLHASPMSADRVVAFMDHIR
  IFQEQVEKLKALHVDSAEYSCLKAIVLFTSDACGLSDAAHIESLQEKSQCALEEYVRSQY
  PNQPSRFGKLLLRLPSLRTVSSSVIEQLFFVRLVGKTPIETLIRDMLLSGSSFNWPYMSI
  QCS
• Function: Coup (chicken ovalbumin upstream promoter) transcription factor binds to the ovalbumin promoter and, in conjunction with another protein (S300-II) stimulates initiation of transcription. Binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses transcriptional activity of LHCG.
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Definitive	Biomarker	[1]
Anxiety disorder	DISBI2BT	Definitive	Biomarker	[1]
Bosch-Boonstra-Schaaf optic atrophy syndrome	DIS4XKXR	Definitive	Autosomal dominant	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Congenital diaphragmatic hernia	DIS0IPVU	Strong	Genetic Variation	[7]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[5]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[10]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[11]
West syndrome	DISLIAU9	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Bladder transitional cell carcinoma	DISNL46A	Disputed	Altered Expression	[13]
Tarsal-carpal coalition syndrome	DISY90L2	Disputed	Biomarker	[13]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	COUP transcription factor 1 (NR2F1) affects the response to substance of DTI-015.	[44]

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 COUP transcription factor 1 (NR2F1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of COUP transcription factor 1 (NR2F1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of COUP transcription factor 1 (NR2F1).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of COUP transcription factor 1 (NR2F1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of COUP transcription factor 1 (NR2F1).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of COUP transcription factor 1 (NR2F1).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COUP transcription factor 1 (NR2F1).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of COUP transcription factor 1 (NR2F1).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of COUP transcription factor 1 (NR2F1).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of COUP transcription factor 1 (NR2F1).	[23]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of COUP transcription factor 1 (NR2F1).	[24]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of COUP transcription factor 1 (NR2F1).	[25]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of COUP transcription factor 1 (NR2F1).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of COUP transcription factor 1 (NR2F1).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of COUP transcription factor 1 (NR2F1).	[28]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of COUP transcription factor 1 (NR2F1).	[29]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of COUP transcription factor 1 (NR2F1).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of COUP transcription factor 1 (NR2F1).	[31]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of COUP transcription factor 1 (NR2F1).	[32]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of COUP transcription factor 1 (NR2F1).	[26]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of COUP transcription factor 1 (NR2F1).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of COUP transcription factor 1 (NR2F1).	[34]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of COUP transcription factor 1 (NR2F1).	[29]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of COUP transcription factor 1 (NR2F1).	[35]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of COUP transcription factor 1 (NR2F1).	[36]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of COUP transcription factor 1 (NR2F1).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of COUP transcription factor 1 (NR2F1).	[40]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of COUP transcription factor 1 (NR2F1).	[41]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of COUP transcription factor 1 (NR2F1).	[42]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of COUP transcription factor 1 (NR2F1).	[43]

References

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• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
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• [15] COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) regulates cell migration and axogenesis in differentiating P19 embryonal carcinoma cells.Mol Endocrinol. 2000 Dec;14(12):1918-33. doi: 10.1210/mend.14.12.0562.
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