Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWOOAM4)

• DOT Name: Interferon alpha-inducible protein 6 (IFI6)
• Synonyms: Interferon-induced protein 6-16; Ifi-6-16
• Gene Name: IFI6
• Related Disease:
  Advanced cancer
  Dengue
  Dermatomyositis
  Hepatitis C virus infection
  Influenza
  Lupus
  Major depressive disorder
  Plasma cell myeloma
  Psoriasis
  Systemic lupus erythematosus
  Breast cancer
  Breast carcinoma
• UniProt ID: IFI6_HUMAN
• Pfam ID: PF06140
• Sequence:
  MRQKAVSLFLCYLLLFTCSGVEAGKKKCSESSDSGSGFWKALTFMAVGGGLAVAGLPALG
  FTGAGIAANSVAASLMSWSAILNGGGVPAGGLVATLQSLGAGGSSVVIGNIGALMGYATH
  KYLDSEEDEE
• Function: Interferon-stimulated protein that plays an important role in innate immune response against a wide variety of viruses. Inhibits flavivirus replication by preventing the formation of virus-induced endoplasmic reticulum membrane invaginations, which are double-membrane vesicles that flaviviruses use for their replication. Has an antiviral activity towards hepatitis C virus/HCV by inhibiting the EGFR signaling pathway, whose activation is required for entry of the virus into cells. Within the nucleus, restricts hepatitis B virus/HBV promoter activity leading to substantial reduction of viral replication and gene expression. Plays a role in apoptosis, negatively regulating the intrinsinc apoptotic signaling pathway and TNFSF10-induced apoptosis. However, it has also been shown to have a pro-apoptotic activity. Modulates innate immune response mediated by RIGI by preventing its activation.
• Reactome Pathway: Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Dengue	DISKH221	Strong	Biomarker	[2]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Lupus	DISOKJWA	Strong	Genetic Variation	[6]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[8]
Psoriasis	DIS59VMN	Strong	Altered Expression	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[10]
Breast cancer	DIS7DPX1	Limited	Biomarker	[11]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interferon alpha-inducible protein 6 (IFI6).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon alpha-inducible protein 6 (IFI6).	[40]

44 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 Interferon alpha-inducible protein 6 (IFI6).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[18]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[23]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interferon alpha-inducible protein 6 (IFI6).	[25]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[26]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[27]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[28]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[29]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[30]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[31]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[32]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[33]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interferon alpha-inducible protein 6 (IFI6).	[34]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[35]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[36]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[37]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[24]
Amantadine	DMS3YE9	Approved	Amantadine increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[23]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[39]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[42]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[43]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon alpha-inducible protein 6 (IFI6).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[46]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[47]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[43]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Interferon alpha-inducible protein 6 (IFI6).	[48]

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