Target Information

Target General Information

Target ID

T35212 (Former ID: TTDI02565)

Target Name

Vascular endothelial cell growth inhibitor (TNFSF15)

Synonyms

Tumor necrosis factor ligand superfamily member 15, secreted form; Tumor necrosis factor ligand superfamily member 15; TNFSF15; TNF ligand-related molecule 1

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Gene Name

TNFSF15

Target Type

Clinical trial target

[1]

Disease

[+] 3 Target-related Diseases

Crohn disease [ICD-11: DD70]

Ulcerative colitis [ICD-11: DD71]

Indeterminate colitis [ICD-11: DD72]

Function

Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.

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BioChemical Class

Cytokine: tumor necrosis factor

UniProt ID

TNF15_HUMAN

Sequence

MAEDLGLSFGETASVEMLPEHGSCRPKARSSSARWALTCCLVLLPFLAGLTTYLLVSQLR
AQGEACVQFQALKGQEFAPSHQQVYAPLRADGDKPRAHLTVVRQTPTQHFKNQFPALHWE
HELGLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRGMTSECSEIRQAGRPNKPDSITVV
ITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAMFSLQEGDKLMVNVSDISLVDYTK
EDKTFFGAFLL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

PRA023

Drug Info

Phase 2

Crohn disease

[2]

TEV-48574

Drug Info

Phase 2

Crohn disease

[3]

PF-07261271

Drug Info

Phase 1

Inflammatory bowel disease

[4]

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
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	2.55E-07
Closeness centrality	1.75E-01	Radiality	1.28E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	5.00E+00	Topological coefficient	5.00E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Early Actions of Anti-Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Drugs on Angiogenic Blood Vessels. Am J Pathol. 2017 Oct;187(10):2337-2347.

REF 2

ClinicalTrials.gov (NCT05013905) A Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of PRA023 in Subjects With Moderately to Severely Active Crohn's Disease. U.S.National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT05668013) A 44-Week Phase 2b Long-Term Extension, RandomizEd, Double-BLind, Study to Determine the Long-Term PharmacokInetics, Efficacy, Safety, and Tolerability of TEV-48574 in Adult PatiEnts With Moderate to Severe Ulcerative Colitis or Crohn's Disease Who Completed the Main Phase of the Dose-Ranging Study (RELIEVE UCCD LTE). U.S.National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT05536440) A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR OPEN, PLACEBO CONTROLLED, DOSE ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE INTRAVENOUS AND MULTIPLE SUBCUTANEOUS AND INTRAVENOUS DOSES OF PF-07261271 IN HEALTHY PARTICIPANTS. U.S.National Institutes of Health.

REF 5

Clinical pipeline report, company report or official report of Prometheus Biosciences

REF 6

Clinical pipeline report, company report or official report of Teva Pharmaceutical

REF 7

Clinical pipeline report, company report or official report of Pfizer

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