Target Information

Target General Information

Target ID

T92124 (Former ID: TTDC00219)

Target Name

OX40L receptor (CD134)

Synonyms

Tumor necrosis factor receptor superfamily member 4; TXGP1L; TAX transcriptionally-activated glycoprotein 1 receptor; CD134; ACT35 antigen

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Gene Name

TNFRSF4

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Atopic eczema [ICD-11: EA80]

Function

Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity.

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UniProt ID

TNR4_HUMAN

Sequence

MCVGARRLGRGPCAALLLLGLGLSTVTGLHCVGDTYPSNDRCCHECRPGNGMVSRCSRSQ
NTVCRPCGPGFYNDVVSSKPCKPCTWCNLRSGSERKQLCTATQDTVCRCRAGTQPLDSYK
PGVDCAPCPPGHFSPGDNQACKPWTNCTLAGKHTLQPASNSSDAICEDRDPPATQPQETQ
GPPARPITVQPTEAWPRTSQGPSTRPVEVPGGRAVAAILGLGLVLGLLGPLAILLALYLL
RRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKI

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3D Structure

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AlphaFold

HIT2.0 ID

T74G3Z

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

Rocatinlimab

Drug Info

Phase 3

Atopic dermatitis

[2]

GBR 830

Drug Info

Phase 2

Atopic dermatitis

[1]

INCAGN01949

Drug Info

Phase 2

Advanced malignancy

[3]

PF-04518600

Drug Info

Phase 2

Solid tumour/cancer

[4]

INCAGN1949

Drug Info

Phase 1/2

Solid tumour/cancer

[5], [6]

Anti-OX40 mab

Drug Info

Phase 1

Prostate cancer

[7]

BGB-A445

Drug Info

Phase 1

Solid tumour/cancer

[8]

MEDI0562

Drug Info

Phase 1

Solid tumour/cancer

[5], [6]

TAK-252

Drug Info

Phase 1

Solid tumour/cancer

[9]

TRemelimumab + MEDI0562

Drug Info

Phase 1

Solid tumour/cancer

[5]

YH002

Drug Info

Phase 1

Aggressive cancer

[10]

Mode of Action

[+] 3 Modes of Action

Antagonist

[+] 1 Antagonist drugs

GBR 830

Drug Info

[1]

Agonist

[+] 6 Agonist drugs

INCAGN01949

Drug Info

[12]

PF-04518600

Drug Info

[5], [6]

INCAGN1949

Drug Info

[5]

MEDI0562

Drug Info

[5], [6]

TAK-252

Drug Info

[15]

TRemelimumab + MEDI0562

Drug Info

[5]

Modulator

[+] 1 Modulator drugs

Anti-OX40 mab

Drug Info

[13]

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Activation-inducible TNFR family receptor (TNFRSF18)		38.710 (24/62)	3.01E-07
Tumor necrosis factor receptor superfamily member 19L (RELT)	PF12606	31.967 (39/122)	4.04E-05
Laminin subunit beta-4 (LAMB4)	PF00053 ; PF00055	34.146 (28/82)	3.08E-04
Laminin subunit alpha-2 (LAMA2)	PF00052 ; PF00053 ; PF00054 ; PF06008 ; PF06009 ; PF00055 More >>	29.204 (33/113)	2.00E-03

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	2.02E-04
Closeness centrality	1.92E-01	Radiality	1.33E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.70E+01	Topological coefficient	5.00E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Cytokine-cytokine receptor interaction

NetPath Pathway

[+] 2 NetPath Pathways

IL2 Signaling Pathway

Wnt Signaling Pathway

PID Pathway

[+] 2 PID Pathways

Downstream signaling in na&#xef

Reactome

[+] 1 Reactome Pathways

TNFs bind their physiological receptors

Target-Related Models and Studies

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Target Validation

Target Validation Info

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 (NCT05633355) A Phase 3, Open-label, 52-week Study to Assess the Safety, Tolerability, and Efficacy of Rocatinlimab (AMG 451) in Adolescent Subjects Aged >= 12 to < 18 Years With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-Orbit). U.S.National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT02923349) A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT03092856) Axitinib With or Without Anti-OX40 Antibody PF-04518600 in Treating Patients With Metastatic Kidney Cancer. U.S. National Institutes of Health.

REF 5

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

REF 6

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

REF 7

OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013 Dec 15;73(24):7189-98.

REF 8

ClinicalTrials.gov (NCT04215978) Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 9

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

REF 10

ClinicalTrials.gov (NCT04353102) A First-in-Human (FIH), Multicenter, Open-Label, Phase 1 Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of YH002 in Subjects With Advanced Solid Malignancies. U.S.National Institutes of Health.

REF 11

An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2023 Jan 21;401(10372):204-214.

REF 12

Sequential therapy with INCAGN01949 followed by ipilimumab and nivolumab in two patients with advanced ovarian carcinoma. Gynecol Oncol Rep. 2020 Oct 1;34:100655.

REF 13

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1873).

REF 14

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

REF 15

Clinical pipeline report, company report or official report of Shattuck Labs.

REF 16

Clinical pipeline report, company report or official report of Biocytogen

REF 17

Clinical pipeline report, company report or official report of Biocytogen

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