Target Information

Target General Information

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Target ID

T40874

Target Name

V-set and immunoglobulin domain-containing protein 9 (TIGIT)

Synonyms

VSTM3; VSIG9; V-set and transmembrane domain-containing protein 3; T-cell immunoreceptor with Ig and ITIM domains

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Gene Name

TIGIT

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Lung cancer [ICD-11: 2C25]

Non-small-cell lung cancer [ICD-11: 2C25]

Function

Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells.

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UniProt ID

TIGIT_HUMAN

Sequence

MRWCLLLIWAQGLRQAPLASGMMTGTIETTGNISAEKGGSIILQCHLSSTTAQVTQVNWE
QQDQLLAICNADLGWHISPSFKDRVAPGPGLGLTLQSLTVNDTGEYFCIYHTYPDGTYTG
RIFLEVLESSVAEHGARFQIPLLGAMAATLVVICTAVIVVVALTRKKKALRIHSVEGDLR
RKSAGQEEWSPSAPSPPGSCVQAEAAPAGLCGEQRGEDCAELHDYFNVLSYRSLGNCSFF
TETG

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 8 Clinical Trial Drugs

AB154

Drug Info

Phase 3

Non-small-cell lung cancer

[2]

Ociperlimab

Drug Info

Phase 3

Non-small-cell lung cancer

[3]

GSK4428859

Drug Info

Phase 2

Aggressive cancer

[4]

Rilvegostomig

Drug Info

Phase 1/2

Non-small-cell lung cancer

[5]

ASP8374

Drug Info

Phase 1

Solid tumour/cancer

[1]

COM902

Drug Info

Phase 1

Solid tumour/cancer

[6]

M6223

Drug Info

Phase 1

Solid tumour/cancer

[7]

SEA-TGT

Drug Info

Phase 1

Solid tumour/cancer

[8]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 4 Inhibitor drugs

AB154

Drug Info

[9]

Ociperlimab

Drug Info

[10]

M6223

Drug Info

[7]

SEA-TGT

Drug Info

[12]

Antagonist

[+] 1 Antagonist drugs

ASP8374

Drug Info

[1]

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	Pathway Map
Cell adhesion molecules	hsa04514	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	7.15E-05
Closeness centrality	1.87E-01	Radiality	1.31E+01	Clustering coefficient	4.00E-01
Neighborhood connectivity	6.80E+00	Topological coefficient	3.00E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Cell adhesion molecules (CAMs)

References

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REF 1

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 2

ClinicalTrials.gov (NCT04736173) Study to Evaluate Monotherapy Compared to Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04746924) A Study of BGB-A1217 With Tislelizumab Compared to Pembrolizumab in Participants With Untreated Lung Cancer. U.S. National Institutes of Health.

REF 4

Clinical pipeline report, company report or official report of GlaxoSmithKline

REF 5

ClinicalTrials.gov (NCT04995523) Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC. U.S.National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT04354246) COM902 (A TIGIT Inhibitor) in Subjects With Advanced Malignancies. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT04457778) First in Human Study of M6223. U.S. National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT04254107) A Safety Study of SEA-TGT (SGN-TGT) in Advanced Cancer. U.S. National Institutes of Health.

REF 9

Clinical pipeline report, company report or official report of Arcus Biosciences.

REF 10

Clinical pipeline report, company report or official report of BeiGene.

REF 11

COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade. Cancer Immunol Immunother. 2021 Apr 26.

REF 12

Clinical pipeline report, company report or official report of Seagen.

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