Target Information

Target General Information

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Target ID

T77664 (Former ID: TTDC00096)

Target Name

Interferon-gamma (IFNG)

Synonyms

Interferon gamma; Immune interferon; IFN-gamma

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Gene Name

IFNG

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Adaptive immunity immunodeficiency [ICD-11: 4A01]

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.

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BioChemical Class

Cytokine: interferon

UniProt ID

IFNG_HUMAN

Sequence

MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ

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3D Structure

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PDB

ADReCS ID

BADD_A03065

HIT2.0 ID

T37VLU

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

Fumaric acid

Drug Info

Phase 3

Multiple sclerosis

[2]

VIR-201

Drug Info

Phase 1/2

Human immunodeficiency virus infection

[3]

AMG 811

Drug Info

Phase 1

Systemic lupus erythematosus

[4]

CIGB-128

Drug Info

Phase 1

Basal cell carcinoma

[5]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

Fontolizumab

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[8]

TAK-603

Drug Info

Discontinued in Phase 2

Inflammatory bowel disease

[9]

Mode of Action

[+] 2 Modes of Action

Binder

[+] 1 Binder drugs

Fumaric acid

Drug Info

[2]

Modulator

[+] 4 Modulator drugs

VIR-201

Drug Info

[11]

AMG 811

Drug Info

[12]

CIGB-128

Drug Info

[13]

TAK-603

Drug Info

[15]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Proteasome	hsa03050	Affiliated Target
Class: Genetic Information Processing => Folding, sorting and degradation	Pathway Hierarchy
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
HIF-1 signaling pathway	hsa04066	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Necroptosis	hsa04217	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
TGF-beta signaling pathway	hsa04350	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Antigen processing and presentation	hsa04612	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Natural killer cell mediated cytotoxicity	hsa04650	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
IL-17 signaling pathway	hsa04657	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Th1 and Th2 cell differentiation	hsa04658	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Th17 cell differentiation	hsa04659	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
T cell receptor signaling pathway	hsa04660	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	13	Degree centrality	1.40E-03	Betweenness centrality	5.11E-05
Closeness centrality	2.28E-01	Radiality	1.40E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	4.12E+01	Topological coefficient	1.36E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 28 KEGG Pathways	+
1	Proteasome
2	Cytokine-cytokine receptor interaction
3	HIF-1 signaling pathway
4	Regulation of autophagy
5	TGF-beta signaling pathway
6	Osteoclast differentiation
7	Antigen processing and presentation
8	Jak-STAT signaling pathway
9	Natural killer cell mediated cytotoxicity
10	T cell receptor signaling pathway
11	Type I diabetes mellitus
12	Salmonella infection
13	Leishmaniasis
14	Chagas disease (American trypanosomiasis)
15	African trypanosomiasis
16	Malaria
17	Toxoplasmosis
18	Amoebiasis
19	Tuberculosis
20	Measles
21	Influenza A
22	Herpes simplex infection
23	Epstein-Barr virus infection
24	Inflammatory bowel disease (IBD)
25	Systemic lupus erythematosus
26	Rheumatoid arthritis
27	Allograft rejection
28	Graft-versus-host disease
NetPath Pathway	[+] 4 NetPath Pathways	+
1	IL1 Signaling Pathway
2	TCR Signaling Pathway
3	IL2 Signaling Pathway
4	Leptin Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	Inflammation mediated by chemokine and cytokine signaling pathway
2	Interferon-gamma signaling pathway
PID Pathway	[+] 16 PID Pathways	+
1	IL27-mediated signaling events
2	IL12-mediated signaling events
3	Calcineurin-regulated NFAT-dependent transcription in lymphocytes
4	SHP2 signaling
5	Regulation of Telomerase
6	Glucocorticoid receptor regulatory network
7	IL2-mediated signaling events
8	IFN-gamma pathway
9	ATF-2 transcription factor network
10	AP-1 transcription factor network
11	IL23-mediated signaling events
12	PDGFR-alpha signaling pathway
13	Calcium signaling in the CD4+ TCR pathway
14	Downstream signaling in na&#xef
15
16	IL12 signaling mediated by STAT4
Reactome	[+] 2 Reactome Pathways	+
1	Interferon gamma signaling
2	Regulation of IFNG signaling
WikiPathways	[+] 16 WikiPathways	+
1	Type II interferon signaling (IFNG)
2	Senescence and Autophagy in Cancer
3	TGF Beta Signaling Pathway
4	Cytokines and Inflammatory Response
5	Hypertrophy Model
6	Inflammatory Response Pathway
7	Aryl Hydrocarbon Receptor Pathway
8	IL1 and megakaryotyces in obesity
9	Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
10	Spinal Cord Injury
11	Allograft Rejection
12	Interferon gamma signaling
13	Proteasome Degradation
14	Folate Metabolism
15	Vitamin B12 Metabolism
16	Selenium Micronutrient Network

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.

REF 2

Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs. 2008 Sep;13(3):465-77.

REF 3

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010310)

REF 4

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028077)

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037683)

REF 6

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025635)

REF 7

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010265)

REF 8

Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006011)

REF 10

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023655)

REF 11

EP patent application no. 17782511, Nucleoside phosphonate conjugates as anti hiv agents.

REF 12

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.

REF 13

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.

REF 14

Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.

REF 15

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.

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