Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK4MYQJ)

• DOT Name: Interferon regulatory factor 9 (IRF9)
• Synonyms: IRF-9; IFN-alpha-responsive transcription factor subunit; ISGF3 p48 subunit; Interferon-stimulated gene factor 3 gamma; ISGF-3 gamma; Transcriptional regulator ISGF3 subunit gamma
• Gene Name: IRF9
• Related Disease:
  Acute myelogenous leukaemia
  Adult glioblastoma
  Glioma
  Nervous system disease
  Subarachnoid hemorrhage
  Breast adenocarcinoma
  Breast cancer
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Esophageal squamous cell carcinoma
  Fibrosarcoma
  Influenza
  Matthew-Wood syndrome
  Mycobacterium infection
  Pneumonitis
  Promyelocytic leukaemia
  Renal cell carcinoma
  Systemic lupus erythematosus
  Transitional cell carcinoma
  Triple negative breast cancer
  Breast carcinoma
  Glioblastoma multiforme
  Herpes simplex encephalitis
  Stroke
  Advanced cancer
  Ebola virus infection
  Gastric cancer
  Hepatitis C virus infection
  Immunodeficiency 65, susceptibility to viral infections
  Melanoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Xeroderma pigmentosum
• UniProt ID: IRF9_HUMAN
• Pfam ID: PF00605 ; PF10401
• Sequence:
  MASGRARCTRKLRNWVVEQVESGQFPGVCWDDTAKTMFRIPWKHAGKQDFREDQDAAFFK
  AWAIFKGKYKEGDTGGPAVWKTRLRCALNKSSEFKEVPERGRMDVAEPYKVYQLLPPGIV
  SGQPGTQKVPSKRQHSSVSSERKEEEDAMQNCTLSPSVLQDSLNNEEEGASGGAVHSDIG
  SSSSSSSPEPQEVTDTTEAPFQGDQRSLEFLLPPEPDYSLLLTFIYNGRVVGEAQVQSLD
  CRLVAEPSGSESSMEQVLFPKPGPLEPTQRLLSQLERGILVASNPRGLFVQRLCPIPISW
  NAPQAPPGPGPHLLPSNECVELFRTAYFCRDLVRYFQGLGPPPKFQVTLNFWEESHGSSH
  TPQNLITVKMEQAFARYLLEQTPEQQAAILSLV
• Function: Transcription factor that plays an essential role in anti-viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.
• KEGG Pathway:
  Necroptosis (hsa04217)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  C-type lectin receptor sig.ling pathway (hsa04625)
  JAK-STAT sig.ling pathway (hsa04630)
  Hepatitis C (hsa05160)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Coro.virus disease - COVID-19 (hsa05171)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[2]
Glioma	DIS5RPEH	Definitive	Biomarker	[3]
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[4]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Altered Expression	[5]
Breast adenocarcinoma	DISMPHJ0	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[10]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[11]
Influenza	DIS3PNU3	Strong	Genetic Variation	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Genetic Variation	[13]
Mycobacterium infection	DISNSMUD	Strong	Biomarker	[14]
Pneumonitis	DIS88E0K	Strong	Genetic Variation	[15]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[18]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[19]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[2]
Herpes simplex encephalitis	DISGX28I	moderate	Genetic Variation	[12]
Stroke	DISX6UHX	moderate	Biomarker	[20]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[21]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[22]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[23]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[24]
Immunodeficiency 65, susceptibility to viral infections	DISDWD8E	Limited	Unknown	[15]
Melanoma	DIS1RRCY	Limited	Altered Expression	[25]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Prostate cancer	DISF190Y	Limited	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[26]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[27]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[23]
Xeroderma pigmentosum	DISQ9H19	Limited	Genetic Variation	[28]

24 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 Interferon regulatory factor 9 (IRF9).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interferon regulatory factor 9 (IRF9).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon regulatory factor 9 (IRF9).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon regulatory factor 9 (IRF9).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interferon regulatory factor 9 (IRF9).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interferon regulatory factor 9 (IRF9).	[34]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon regulatory factor 9 (IRF9).	[35]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interferon regulatory factor 9 (IRF9).	[36]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Interferon regulatory factor 9 (IRF9).	[37]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interferon regulatory factor 9 (IRF9).	[38]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Interferon regulatory factor 9 (IRF9).	[39]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interferon regulatory factor 9 (IRF9).	[40]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Interferon regulatory factor 9 (IRF9).	[41]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon regulatory factor 9 (IRF9).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Interferon regulatory factor 9 (IRF9).	[43]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Interferon regulatory factor 9 (IRF9).	[31]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon regulatory factor 9 (IRF9).	[44]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Interferon regulatory factor 9 (IRF9).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interferon regulatory factor 9 (IRF9).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interferon regulatory factor 9 (IRF9).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interferon regulatory factor 9 (IRF9).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interferon regulatory factor 9 (IRF9).	[38]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Interferon regulatory factor 9 (IRF9).	[47]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Interferon regulatory factor 9 (IRF9).	[43]

References

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