Details of Drug Off-Target (DOT)

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

• DOT Name: Interferon gamma receptor 1 (IFNGR1)
• Synonyms: IFN-gamma receptor 1; IFN-gamma-R1; CDw119; Interferon gamma receptor alpha-chain; IFN-gamma-R-alpha; CD antigen CD119
• Gene Name: IFNGR1
• Related Disease:
  B-cell neoplasm
  Adenocarcinoma
  Atopic dermatitis
  Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
  Carcinoma of esophagus
  Cataract
  Chronic hepatitis B virus infection
  Colitis
  Colorectal carcinoma
  Crohn disease
  Cystic fibrosis
  Eclampsia
  Endometriosis
  Esophageal cancer
  Hepatitis C virus infection
  Herpes simplex infection
  Hyperinsulinemia
  Immunodeficiency 27A
  Inborn error of immunity
  Inflammatory bowel disease
  Influenza
  Mycobacterium infection
  Myocardial ischemia
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Plasmodium falciparum malaria
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Ulcerative colitis
  Zika virus infection
  Breast cancer
  Breast carcinoma
  Osteomyelitis
  Visceral leishmaniasis
  Autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
  Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency
  Amyotrophic lateral sclerosis
  Multiple sclerosis
  Advanced cancer
  Bacterial infection
  Colon cancer
  Colon carcinoma
  Hepatitis B virus infection
  Malaria
  Myasthenia gravis
  Prostate cancer
  Rectal carcinoma
• UniProt ID: INGR1_HUMAN
• PDB ID: 1FG9; 1FYH; 1JRH; 6E3K; 6E3L
• Pfam ID: PF07140 ; PF20634 ; PF01108
• Sequence:
  MALLFLLPLVMQGVSRAEMGTADLGPSSVPTPTNVTIESYNMNPIVYWEYQIMPQVPVFT
  VEVKNYGVKNSEWIDACINISHHYCNISDHVGDPSNSLWVRVKARVGQKESAYAKSEEFA
  VCRDGKIGPPKLDIRKEEKQIMIDIFHPSVFVNGDEQEVDYDPETTCYIRVYNVYVRMNG
  SEIQYKILTQKEDDCDEIQCQLAIPVSSLNSQYCVSAEGVLHVWGVTTEKSKEVCITIFN
  SSIKGSLWIPVVAALLLFLVLSLVFICFYIKKINPLKEKSIILPKSLISVVRSATLETKP
  ESKYVSLITSYQPFSLEKEVVCEEPLSPATVPGMHTEDNPGKVEHTEELSSITEVVTTEE
  NIPDVVPGSHLTPIERESSSPLSSNQSEPGSIALNSYHSRNCSESDHSRNGFDTDSSCLE
  SHSSLSDSEFPPNNKGEIKTEGQELITVIKAPTSFGYDKPHVLVDLLVDDSGKESLIGYR
  PTEDSKEFS
• Function: Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Associates with transmembrane accessory factor IFNGR2 to form a functional receptor. Upon ligand binding, the intracellular domain of IFNGR1 opens out to allow association of downstream signaling components JAK1 and JAK2. In turn, activated JAK1 phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to dimerization, translocation to the nucleus, and stimulation of target gene transcription. STAT3 can also be activated in a similar manner although activation seems weaker. IFNGR1 intracellular domain phosphorylation also provides a docking site for SOCS1 that regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 sig.ling pathway (hsa04066)
  Necroptosis (hsa04217)
  Osteoclast differentiation (hsa04380)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Influenza A (hsa05164)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Pathways in cancer (hsa05200)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway:
  Regulation of IFNG signaling (R-HSA-877312)
  Potential therapeutics for SARS (R-HSA-9679191)
  IFNG signaling activates MAPKs (R-HSA-9732724)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[3]
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	DISNY5AW	Strong	Autosomal dominant	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Cataract	DISUD7SL	Strong	Genetic Variation	[6]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Genetic Variation	[7]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[9]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Eclampsia	DISWPO8U	Strong	Genetic Variation	[12]
Endometriosis	DISX1AG8	Strong	Biomarker	[13]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[14]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[15]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[16]
Immunodeficiency 27A	DIS7ZWZK	Strong	Autosomal recessive	[17]
Inborn error of immunity	DISNGCMN	Strong	Genetic Variation	[18]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[10]
Influenza	DIS3PNU3	Strong	Biomarker	[19]
Mycobacterium infection	DISNSMUD	Strong	Genetic Variation	[20]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[21]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Obesity	DIS47Y1K	Strong	Biomarker	[16]
Osteoporosis	DISF2JE0	Strong	Biomarker	[23]
Plasmodium falciparum malaria	DIS3Q9KF	Strong	Genetic Variation	[24]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[27]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[10]
Zika virus infection	DISQUCTY	Strong	Biomarker	[28]
Breast cancer	DIS7DPX1	moderate	Biomarker	[29]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[29]
Osteomyelitis	DIS0VUZL	moderate	Genetic Variation	[30]
Visceral leishmaniasis	DISTKEYK	moderate	Altered Expression	[31]
Autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	DISH4NG8	Supportive	Autosomal recessive	[32]
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency	DIS419ET	Supportive	Autosomal recessive	[32]
Amyotrophic lateral sclerosis	DISF7HVM	Disputed	Biomarker	[33]
Multiple sclerosis	DISB2WZI	Disputed	Genetic Variation	[34]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[35]
Bacterial infection	DIS5QJ9S	Limited	Altered Expression	[36]
Colon cancer	DISVC52G	Limited	Genetic Variation	[37]
Colon carcinoma	DISJYKUO	Limited	Genetic Variation	[37]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[7]
Malaria	DISQ9Y50	Limited	Genetic Variation	[38]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[39]
Prostate cancer	DISF190Y	Limited	Biomarker	[40]
Rectal carcinoma	DIS8FRR7	Limited	Genetic Variation	[37]

3 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 gamma receptor 1 (IFNGR1).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Interferon gamma receptor 1 (IFNGR1).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Interferon gamma receptor 1 (IFNGR1).	[64]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interferon gamma receptor 1 (IFNGR1).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon gamma receptor 1 (IFNGR1).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interferon gamma receptor 1 (IFNGR1).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon gamma receptor 1 (IFNGR1).	[47]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interferon gamma receptor 1 (IFNGR1).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Interferon gamma receptor 1 (IFNGR1).	[49]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interferon gamma receptor 1 (IFNGR1).	[51]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[52]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[53]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Interferon gamma receptor 1 (IFNGR1).	[54]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Interferon gamma receptor 1 (IFNGR1).	[55]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interferon gamma receptor 1 (IFNGR1).	[56]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Interferon gamma receptor 1 (IFNGR1).	[57]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Interferon gamma receptor 1 (IFNGR1).	[58]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[59]
Pentamidine	DMHZJCG	Approved	Pentamidine increases the expression of Interferon gamma receptor 1 (IFNGR1).	[56]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Interferon gamma receptor 1 (IFNGR1).	[60]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate increases the expression of Interferon gamma receptor 1 (IFNGR1).	[56]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[61]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Interferon gamma receptor 1 (IFNGR1).	[62]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Interferon gamma receptor 1 (IFNGR1).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[65]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interferon gamma receptor 1 (IFNGR1).	[66]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[67]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[68]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Interferon gamma receptor 1 (IFNGR1).	[69]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Interferon gamma receptor 1 (IFNGR1).	[70]

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