Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC1A2PQ)

• DOT Name: Interferon regulatory factor 7 (IRF7)
• Synonyms: IRF-7
• Gene Name: IRF7
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adult lymphoma
  Advanced cancer
  Allergic asthma
  Alzheimer disease
  Asthma
  Astrocytoma
  Autoimmune disease
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  HIV infectious disease
  Immunodeficiency
  Influenza
  Kaposi sarcoma
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lupus
  Major depressive disorder
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Pediatric lymphoma
  Prostate cancer
  Prostate carcinoma
  Systemic lupus erythematosus
  Systemic sclerosis
  Tuberculosis
  Type-1 diabetes
  Bacterial infection
  Lymphoma
  Obesity
  Pulmonary disease
  Squamous cell carcinoma
  Chronic obstructive pulmonary disease
  Graves disease
  Immunodeficiency 39
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Type-1/2 diabetes
• UniProt ID: IRF7_HUMAN
• PDB ID: 2O61
• Pfam ID: PF00605 ; PF10401
• Sequence:
  MALAPERAAPRVLFGEWLLGEISSGCYEGLQWLDEARTCFRVPWKHFARKDLSEADARIF
  KAWAVARGRWPPSSRGGGPPPEAETAERAGWKTNFRCALRSTRRFVMLRDNSGDPADPHK
  VYALSRELCWREGPGTDQTEAEAPAAVPPPQGGPPGPFLAHTHAGLQAPGPLPAPAGDKG
  DLLLQAVQQSCLADHLLTASWGADPVPTKAPGEGQEGLPLTGACAGGPGLPAGELYGWAV
  ETTPSPGPQPAALTTGEAAAPESPHQAEPYLSPSPSACTAVQEPSPGALDVTIMYKGRTV
  LQKVVGHPSCTFLYGPPDPAVRATDPQQVAFPSPAELPDQKQLRYTEELLRHVAPGLHLE
  LRGPQLWARRMGKCKVYWEVGGPPGSASPSTPACLLPRNCDTPIFDFRVFFQELVEFRAR
  QRRGSPRYTIYLGFGQDLSAGRPKEKSLVLVKLEPWLCRVHLEGTQREGVSSLDSSSLSL
  CLSSANSLYDDIECFLMELEQPA
• Function: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.
• Tissue Specificity: Expressed predominantly in spleen, thymus and peripheral blood leukocytes.
• KEGG Pathway:
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Cytosolic D.-sensing pathway (hsa04623)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Viral carcinogenesis (hsa05203)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Interferon gamma signaling (R-HSA-877300)
  TICAM1-dependent activation of IRF3/IRF7 (R-HSA-9013973)
  Interferon alpha/beta signaling (R-HSA-909733)
  TRAF3-dependent IRF activation pathway (R-HSA-918233)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  Activation of IRF3, IRF7 mediated by TBK1, IKK (IKBKE) (R-HSA-936964)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling (R-HSA-975110)
  DEx/H-box helicases activate type I IFN and inflammatory cytokines production (R-HSA-3134963)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Allergic asthma	DISHF0H3	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[5]
Asthma	DISW9QNS	Strong	Altered Expression	[4]
Astrocytoma	DISL3V18	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[11]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[14]
HIV infectious disease	DISO97HC	Strong	Biomarker	[15]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[16]
Influenza	DIS3PNU3	Strong	Genetic Variation	[17]
Kaposi sarcoma	DISC1H1Z	Strong	Biomarker	[18]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Lupus	DISOKJWA	Strong	Biomarker	[21]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[22]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[23]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[25]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[26]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[27]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[28]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[29]
Lymphoma	DISN6V4S	moderate	Biomarker	[2]
Obesity	DIS47Y1K	moderate	Altered Expression	[30]
Pulmonary disease	DIS6060I	moderate	Genetic Variation	[31]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[32]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[33]
Graves disease	DISU4KOQ	Limited	Genetic Variation	[34]
Immunodeficiency 39	DIS89D2G	Limited	Autosomal recessive	[35]
Melanoma	DIS1RRCY	Limited	Altered Expression	[36]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[37]
Neoplasm	DISZKGEW	Limited	Posttranslational Modification	[9]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Interferon regulatory factor 7 (IRF7) affects the response to substance of Mitoxantrone.	[67]

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 Interferon regulatory factor 7 (IRF7).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Interferon regulatory factor 7 (IRF7).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon regulatory factor 7 (IRF7).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon regulatory factor 7 (IRF7).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interferon regulatory factor 7 (IRF7).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon regulatory factor 7 (IRF7).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon regulatory factor 7 (IRF7).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interferon regulatory factor 7 (IRF7).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interferon regulatory factor 7 (IRF7).	[46]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Interferon regulatory factor 7 (IRF7).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interferon regulatory factor 7 (IRF7).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Interferon regulatory factor 7 (IRF7).	[48]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon regulatory factor 7 (IRF7).	[49]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon regulatory factor 7 (IRF7).	[49]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Interferon regulatory factor 7 (IRF7).	[48]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon regulatory factor 7 (IRF7).	[49]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Interferon regulatory factor 7 (IRF7).	[50]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon regulatory factor 7 (IRF7).	[49]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon regulatory factor 7 (IRF7).	[51]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Interferon regulatory factor 7 (IRF7).	[52]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Interferon regulatory factor 7 (IRF7).	[53]
Jakafi	DMNORK8	Phase 3	Jakafi decreases the expression of Interferon regulatory factor 7 (IRF7).	[51]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Interferon regulatory factor 7 (IRF7).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Interferon regulatory factor 7 (IRF7).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interferon regulatory factor 7 (IRF7).	[57]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Interferon regulatory factor 7 (IRF7).	[58]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Interferon regulatory factor 7 (IRF7).	[59]
BIX-01294	DM5CBNY	Preclinical	BIX-01294 increases the expression of Interferon regulatory factor 7 (IRF7).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interferon regulatory factor 7 (IRF7).	[61]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interferon regulatory factor 7 (IRF7).	[62]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Interferon regulatory factor 7 (IRF7).	[63]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Interferon regulatory factor 7 (IRF7).	[64]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Interferon regulatory factor 7 (IRF7).	[65]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Interferon regulatory factor 7 (IRF7).	[66]

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