Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXG9JM7)

• DOT Name: Interferon gamma (IFNG)
• Synonyms: IFN-gamma; Immune interferon
• Gene Name: IFNG
• Related Disease: Immunodeficiency 69
• UniProt ID: IFNG_HUMAN
• PDB ID: 1EKU; 1FG9; 1FYH; 1HIG; 3BES; 6E3K; 6E3L
• Pfam ID: PF00714
• Sequence:
  MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
  EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
  YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ
• Function: Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL. Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation.
• Tissue Specificity: Released primarily from activated T lymphocytes.
• KEGG Pathway:
  Proteasome (hsa03050)
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 sig.ling pathway (hsa04066)
  Necroptosis (hsa04217)
  TGF-beta sig.ling pathway (hsa04350)
  Osteoclast differentiation (hsa04380)
  Antigen processing and presentation (hsa04612)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  Type I diabetes mellitus (hsa04940)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Influenza A (hsa05164)
  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)
  Systemic lupus erythematosus (hsa05322)
  Rheumatoid arthritis (hsa05323)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Regulation of IFNG signaling (R-HSA-877312)
  RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  IFNG signaling activates MAPKs (R-HSA-9732724)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 69	DIS0VCMG	Limited	Unknown	[1]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Interferon gamma (IFNG) increases the abundance of Fluorouracil.	[73]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Plevitrexed	DM7Y60I	Phase 2	Interferon gamma (IFNG) increases the response to substance of Plevitrexed.	[74]

19 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the secretion of Interferon gamma (IFNG).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the secretion of Interferon gamma (IFNG).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the secretion of Interferon gamma (IFNG).	[10]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the secretion of Interferon gamma (IFNG).	[22]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the secretion of Interferon gamma (IFNG).	[29]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the secretion of Interferon gamma (IFNG).	[30]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the secretion of Interferon gamma (IFNG).	[31]
Budesonide	DMJIBAW	Approved	Budesonide decreases the secretion of Interferon gamma (IFNG).	[37]
Ethambutol	DMR87LC	Approved	Ethambutol increases the secretion of Interferon gamma (IFNG).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the secretion of Interferon gamma (IFNG).	[42]
Cilomilast	DMHSM7I	Discontinued in Phase 3	Cilomilast decreases the secretion of Interferon gamma (IFNG).	[50]
Methylthioadenosine	DMC8J6F	Terminated	Methylthioadenosine decreases the secretion of Interferon gamma (IFNG).	[52]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the secretion of Interferon gamma (IFNG).	[59]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the secretion of Interferon gamma (IFNG).	[2]
acrolein	DMAMCSR	Investigative	acrolein decreases the secretion of Interferon gamma (IFNG).	[59]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the secretion of Interferon gamma (IFNG).	[64]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol affects the secretion of Interferon gamma (IFNG).	[67]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione increases the secretion of Interferon gamma (IFNG).	[29]
EPZ015666	DM3INX7	Investigative	EPZ015666 decreases the secretion of Interferon gamma (IFNG).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interferon gamma (IFNG).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interferon gamma (IFNG).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Interferon gamma (IFNG).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interferon gamma (IFNG).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interferon gamma (IFNG).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon gamma (IFNG).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Interferon gamma (IFNG).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interferon gamma (IFNG).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interferon gamma (IFNG).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Interferon gamma (IFNG).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Interferon gamma (IFNG).	[15]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Interferon gamma (IFNG).	[16]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Interferon gamma (IFNG).	[17]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Interferon gamma (IFNG).	[18]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Interferon gamma (IFNG).	[19]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Interferon gamma (IFNG).	[20]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Interferon gamma (IFNG).	[21]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of Interferon gamma (IFNG).	[23]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Interferon gamma (IFNG).	[24]
Thalidomide	DM70BU5	Approved	Thalidomide affects the expression of Interferon gamma (IFNG).	[25]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Interferon gamma (IFNG).	[26]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Interferon gamma (IFNG).	[27]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Interferon gamma (IFNG).	[28]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid affects the expression of Interferon gamma (IFNG).	[32]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Interferon gamma (IFNG).	[33]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of Interferon gamma (IFNG).	[34]
Cimetidine	DMH61ZB	Approved	Cimetidine increases the expression of Interferon gamma (IFNG).	[35]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Interferon gamma (IFNG).	[36]
Ergotidine	DM78IME	Approved	Ergotidine affects the expression of Interferon gamma (IFNG).	[17]
Lamivudine	DMI347A	Approved	Lamivudine increases the expression of Interferon gamma (IFNG).	[38]
Dydrogesterone	DMAKIDV	Approved	Dydrogesterone decreases the expression of Interferon gamma (IFNG).	[39]
Betamethasone valerate	DMMIAXO	Approved	Betamethasone valerate decreases the expression of Interferon gamma (IFNG).	[33]
Pimecrolimus	DMZLGRB	Approved	Pimecrolimus decreases the expression of Interferon gamma (IFNG).	[40]
Lisuride	DMCME17	Approved	Lisuride increases the expression of Interferon gamma (IFNG).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interferon gamma (IFNG).	[43]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interferon gamma (IFNG).	[44]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Interferon gamma (IFNG).	[45]
Apilimod dimesylate	DM4N2O0	Phase 2	Apilimod dimesylate decreases the expression of Interferon gamma (IFNG).	[46]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate decreases the expression of Interferon gamma (IFNG).	[47]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the expression of Interferon gamma (IFNG).	[49]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Interferon gamma (IFNG).	[12]
MCPP	DMIG5W8	Discontinued in Phase 2	MCPP decreases the expression of Interferon gamma (IFNG).	[51]
Acteoside	DM0YHKB	Terminated	Acteoside decreases the expression of Interferon gamma (IFNG).	[43]
Gliotoxin	DMONQYZ	Terminated	Gliotoxin decreases the expression of Interferon gamma (IFNG).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interferon gamma (IFNG).	[54]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon gamma (IFNG).	[55]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Interferon gamma (IFNG).	[56]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Interferon gamma (IFNG).	[57]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Interferon gamma (IFNG).	[58]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Interferon gamma (IFNG).	[60]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl affects the expression of Interferon gamma (IFNG).	[61]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Interferon gamma (IFNG).	[62]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid increases the expression of Interferon gamma (IFNG).	[63]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the expression of Interferon gamma (IFNG).	[65]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of Interferon gamma (IFNG).	[62]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid increases the expression of Interferon gamma (IFNG).	[66]
PATULIN	DM0RV9C	Investigative	PATULIN decreases the expression of Interferon gamma (IFNG).	[53]
Ginsenoside Re	DM46FVD	Investigative	Ginsenoside Re decreases the expression of Interferon gamma (IFNG).	[68]
Irbesartan	DMTP1DC	Investigative	Irbesartan decreases the expression of Interferon gamma (IFNG).	[69]
CYANATE	DM6HQDL	Investigative	CYANATE increases the expression of Interferon gamma (IFNG).	[70]
methyl isocyanate	DME4JGF	Investigative	methyl isocyanate increases the expression of Interferon gamma (IFNG).	[71]
Clobenpropit	DM537OH	Investigative	Clobenpropit affects the expression of Interferon gamma (IFNG).	[17]
Dimaprit	DMA4NI2	Investigative	Dimaprit affects the expression of Interferon gamma (IFNG).	[17]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Investigative	ISOPENTENYL PYROPHOSPHATE increases the expression of Interferon gamma (IFNG).	[72]
4-methylhistamine	DMABMPQ	Investigative	4-methylhistamine affects the expression of Interferon gamma (IFNG).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon gamma (IFNG).	[48]

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