Target Information
Target General Information | Top | |||||
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Target ID |
T46084
(Former ID: TTDI02193)
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Target Name |
TNF related apoptosis inducing ligand (TNFSF10)
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Synonyms |
Tumor necrosis factor ligand superfamily member 10; TRAIL; TNF-related apoptosis-inducing ligand; Protein TRAIL; CD253; Apo-2L; Apo-2 ligand; APO2L
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Gene Name |
TNFSF10
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 4 Target-related Diseases | + | ||||
1 | Brain cancer [ICD-11: 2A00] | |||||
2 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
3 | Prostate cancer [ICD-11: 2C82] | |||||
4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis. Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG.
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BioChemical Class |
Cytokine: tumor necrosis factor
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UniProt ID | ||||||
Sequence |
MAMMEVQGGPSLGQTCVLIVIFTVLLQSLCVAVTYVYFTNELKQMQDKYSKSGIACFLKE
DDSYWDPNDEESMNSPCWQVKWQLRQLVRKMILRTSEETISTVQEKQQNISPLVRERGPQ RVAAHITGTRGRSNTLSSPNSKNEKALGRKINSWESSRSGHSFLSNLHLRNGELVIHEKG FYYIYSQTYFRFQEEIKENTKNDKQMVQYIYKYTSYPDPILLMKSARNSCWSKDAEYGLY SIYQGGIFELKENDRIFVSVTNEHLIDMDHEASFFGAFLVG Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T92LK2 |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Ad5-TRAIL | Drug Info | Phase 1 | Prostate cancer | [4] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | Nimesulide | Drug Info | Terminated | Metastatic colorectal cancer | [5] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | Ad5-TRAIL | Drug Info | [6] | |||
2 | Nimesulide | Drug Info | [7] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Viral protein interaction with cytokine and cytokine receptor | hsa04061 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
FoxO signaling pathway | hsa04068 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Apoptosis | hsa04210 | Affiliated Target |
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Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
Necroptosis | hsa04217 | Affiliated Target |
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Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
Natural killer cell mediated cytotoxicity | hsa04650 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 12 | Degree centrality | 1.29E-03 | Betweenness centrality | 2.49E-04 |
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Closeness centrality | 2.20E-01 | Radiality | 1.39E+01 | Clustering coefficient | 6.67E-01 |
Neighborhood connectivity | 2.99E+01 | Topological coefficient | 1.94E-01 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 6 KEGG Pathways | + | ||||
1 | Cytokine-cytokine receptor interaction | |||||
2 | FoxO signaling pathway | |||||
3 | Apoptosis | |||||
4 | Natural killer cell mediated cytotoxicity | |||||
5 | Measles | |||||
6 | Influenza A | |||||
NetPath Pathway | [+] 5 NetPath Pathways | + | ||||
1 | IL2 Signaling Pathway | |||||
2 | IL4 Signaling Pathway | |||||
3 | TGF_beta_Receptor Signaling Pathway | |||||
4 | TNFalpha Signaling Pathway | |||||
5 | Leptin Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Apoptosis signaling pathway | |||||
PID Pathway | [+] 2 PID Pathways | + | ||||
1 | TRAIL signaling pathway | |||||
2 | Caspase Cascade in Apoptosis | |||||
Reactome | [+] 6 Reactome Pathways | + | ||||
1 | Ligand-dependent caspase activation | |||||
2 | Regulation by c-FLIP | |||||
3 | RIPK1-mediated regulated necrosis | |||||
4 | CASP8 activity is inhibited | |||||
5 | Dimerization of procaspase-8 | |||||
6 | TRAIL signaling | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | Apoptosis | |||||
2 | Extrinsic Pathway for Apoptosis | |||||
3 | Apoptosis Modulation and Signaling | |||||
4 | TP53 Network |
References | Top | |||||
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REF 1 | Cancer gene therapy using a novel secretable trimeric TRAIL. Gene Ther. 2006 Feb;13(4):330-8. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026657) | |||||
REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 4 | Phase I trial of Ad5-TRAIL-mediated gene transfer in men with locally-confined prostate cancer prior to planned radical prostatectomy. The Journal of Urology. 04/2008; 179(4):396-396. | |||||
REF 5 | Clinical pipeline report, company report or official report of Genentech (2011). | |||||
REF 6 | Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone deacetylase inhibitors. Cancer Gene Ther. 2006 Jun;13(6):628-32. | |||||
REF 7 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. |
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