Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXO5MHZ)

• DOT Name: Interferon epsilon (IFNE)
• Synonyms: IFN-epsilon; Interferon epsilon-1
• Gene Name: IFNE
• Related Disease:
  Bladder cancer
  Hepatitis C virus infection
  Urinary bladder cancer
  Urinary bladder neoplasm
  Vitiligo
  Bacterial infection
  Breast cancer
  Breast carcinoma
  Coronary heart disease
  Sexually transmitted infection
• UniProt ID: IFNE_HUMAN
• Pfam ID: PF00143
• Sequence:
  MIIKHFFGTVLVLLASTTIFSLDLKLIIFQQRQVNQESLKLLNKLQTLSIQQCLPHRKNF
  LLPQKSLSPQQYQKGHTLAILHEMLQQIFSLFRANISLDGWEENHTEKFLIQLHQQLEYL
  EALMGLEAEKLSGTLGSDNLRLQVKMYFRRIHDYLENQDYSTCAWAIVQVEISRCLFFVF
  SLTEKLSKQGRPLNDMKQELTTEFRSPR
• Function: Type I interferon required for maintaining basal levels of IFN-regulated genes, including 2'-5'-oligoadenylate synthetase, IRF7 and ISG15, in the female reproductive tract. Directly mediates protection against viral and bacterial genital infections.
• Tissue Specificity: Endometrium-specific.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  JAK-STAT sig.ling pathway (hsa04630)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Altered Expression	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[2]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[1]
Vitiligo	DISR05SL	Strong	Genetic Variation	[3]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[6]
Sexually transmitted infection	DISIVIAL	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interferon epsilon (IFNE).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Interferon epsilon (IFNE).	[9]

References

• [1] Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.Oncogene. 2017 Jan 5;36(1):35-46. doi: 10.1038/onc.2016.172. Epub 2016 Jun 6.
• [2] HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFN2a and Ribavirin: a randomized controlled trial.J Viral Hepat. 2014 Jul;21(7):458-65. doi: 10.1111/jvh.12163. Epub 2013 Aug 27.
• [3] Association study between nonsense polymorphism (rs2039381, Gln71Stop) of interferon- and susceptibility to vitiligo in Korean population.Immunol Invest. 2013;42(5):423-30. doi: 10.3109/08820139.2013.804836.
• [4] Interferon- protects the female reproductive tract from viral and bacterial infection.Science. 2013 Mar 1;339(6123):1088-92. doi: 10.1126/science.1233321.
• [5] The Arabian camel, Camelus dromedarius interferon epsilon: Functional expression, in vitro refolding, purification and cytotoxicity on breast cancer cell lines.PLoS One. 2019 Sep 6;14(9):e0213880. doi: 10.1371/journal.pone.0213880. eCollection 2019.
• [6] Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.Circulation. 2008 Apr 1;117(13):1675-84. doi: 10.1161/CIRCULATIONAHA.107.730614. Epub 2008 Mar 24.
• [7] Interferon epsilon in the reproductive tract of healthy and genital herpes simplex virus-infected pregnant women: Results of a pilot study.Am J Reprod Immunol. 2018 Sep;80(3):e12995. doi: 10.1111/aji.12995. Epub 2018 Jun 14.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.