Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT93WF5)

• DTT Name: Interferon-gamma (IFNG)
• Synonyms: Interferon gamma; Immune interferon; IFN-gamma
• Gene Name: IFNG
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: interferon
• UniProt ID: IFNG_HUMAN
• TTD ID: T77664
• Sequence:
  MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
  EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
  YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ
• Function: Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
• KEGG Pathway:
  Proteasome (hsa03050)
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 signaling pathway (hsa04066)
  Regulation of autophagy (hsa04140)
  TGF-beta signaling pathway (hsa04350)
  Osteoclast differentiation (hsa04380)
  Antigen processing and presentation (hsa04612)
  Jak-STAT signaling pathway (hsa04630)
  Natural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor signaling pathway (hsa04660)
  Type I diabetes mellitus (hsa04940)
  Salmonella infection (hsa05132)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Inflammatory bowel disease (IBD) (hsa05321)
  Systemic lupus erythematosus (hsa05322)
  Rheumatoid arthritis (hsa05323)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
• Reactome Pathway:
  Regulation of IFNG signaling (R-HSA-877312)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Emapalumab	DMZG5WL	Primary haemophagocytic lymphohistiocytosis	4A01.23	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fumaric acid	DMP83UZ	Multiple sclerosis	8A40	Phase 3	[2]
VIR-201	DMAMIU4	Human immunodeficiency virus infection	1C62	Phase 1/2	[3]
AMG 811	DMEIMBP	Discoid lupus erythematosus	EB51.0	Phase 1	[4]
CIGB-128	DMB2MKU	Basal cell carcinoma	2C32	Phase 1	[5]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CRx-191	DMB9QSJ	Psoriatic disorder	EA90	Discontinued in Phase 2	[6]
Fontolizumab	DMEH6LV	Inflammatory bowel disease	DD72	Discontinued in Phase 2	[7]
TAK-603	DMN1YHP	Inflammatory bowel disease	DD72	Discontinued in Phase 2	[8]
TG-1042	DMS4BUK	B-cell lymphoma	2A86	Discontinued in Phase 2	[9]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VPM-4-001	DMZHAVG	Prostate cancer	2C82.0	Preclinical	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	3.56E-01	-2.90E-03	-0.01
Prostate cancer	2C82	Prostate	3.25E-01	0.02	0.04

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs. 2008 Sep;13(3):465-77.
• [3] EP patent application no. 17782511, Nucleoside phosphonate conjugates as anti hiv agents.
• [4] Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-gamma IgG1 monoclonal antibody, in patients with systemic lupus erythematosus. Pharm Res. 2015 Feb;32(2):640-53.
• [5] Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial.BMC Pharmacol Toxicol.2012 Dec 28;13:20.
• [6] CombinatoRx Drug Candidate CRx-191 Demonstrates Positive Phase 2 Results In Psoriasis. CombinatoRx. 2008.
• [7] Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.
• [8] T helper 1 inhibitor TAK-603 inhibits IFN-gamma and IL-12 production with no effect on IL-18: an observation in sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis. 2004 Oct;21(3):204-11.
• [9] Drug evaluation: TG-1042, an adenovirus-mediated IFNgamma gene delivery for the intratumoral therapy of primary cutaneous lymphomas. Curr Opin Investig Drugs. 2007 Jun;8(6):493-8.
• [10] BioPartnering North America--Programs from Pharma in Europe and the Middle East. IDrugs. 2010 Mar;13(3):162-5.