Target Information
| Target General Information | Top | |||||
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| Target ID |
T77645
(Former ID: TTDC00267)
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| Target Name |
TRAIL receptor 1 (TRAIL-R1)
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| Synonyms |
Tumor necrosis factor receptor superfamily member 10A; TRAILR1; TNF-related apoptosis-inducing ligand receptor 1; Death receptor 4; DR4; CD261; APO2
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| Gene Name |
TNFRSF10A
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Lung cancer [ICD-11: 2C25] | |||||
| Function |
The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Receptor for the cytotoxic ligand TNFSF10/TRAIL.
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| BioChemical Class |
Cytokine receptor
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| UniProt ID | ||||||
| Sequence |
MAPPPARVHLGAFLAVTPNPGSAASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMG
QHGPSARARAGRAPGPRPAREASPRLRVHKTFKFVVVGVLLQVVPSSAATIKLHDQSIGT QQWEHSPLGELCPPGSHRSEHPGACNRCTEGVGYTNASNNLFACLPCTACKSDEEERSPC TTTRNTACQCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIECVHKESGNGHNI WVILVVTLVVPLLLVAVLIVCCCIGSGCGGDPKCMDRVCFWRLGLLRGPGAEDNAHNEIL SNADSLSTFVSEQQMESQEPADLTGVTVQSPGEAQCLLGPAEAEGSQRRRLLVPANGADP TETLMLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTG RNASIHTLLDALERMEERHAREKIQDLLVDSGKFIYLEDGTGSAVSLE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T62USB | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Mapatumumab | Drug Info | Phase 2 | Non-small-cell lung cancer | [2] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | RhApo2L/TRAIL | Drug Info | Discontinued in Phase 1/2 | Solid tumour/cancer | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Mapatumumab | Drug Info | [1] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | RhApo2L/TRAIL | Drug Info | [4], [5] | |||
| 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 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
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There is no similarity protein (E value < 0.005) for this target
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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 | ||
| p53 signaling pathway | hsa04115 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | 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 | 2.73E-04 |
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| Closeness centrality | 2.40E-01 | Radiality | 1.42E+01 | Clustering coefficient | 6.97E-01 |
| Neighborhood connectivity | 5.53E+01 | Topological coefficient | 1.29E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| 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 | [+] 5 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | Apoptosis | |||||
| 3 | Natural killer cell mediated cytotoxicity | |||||
| 4 | Measles | |||||
| 5 | Influenza A | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Apoptosis signaling pathway | |||||
| 2 | p53 pathway | |||||
| PID Pathway | [+] 3 PID Pathways | + | ||||
| 1 | TRAIL signaling pathway | |||||
| 2 | Direct p53 effectors | |||||
| 3 | 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 | [+] 2 WikiPathways | + | ||||
| 1 | miR-targeted genes in lymphocytes - TarBase | |||||
| 2 | Apoptosis Modulation and Signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | National Cancer Institute Drug Dictionary (drug id 486626). | |||||
| REF 2 | ClinicalTrials.gov (NCT00094848) Study of TRM-1 (TRAIL-R1 Monoclonal Antibody) in Subjects With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL). U.S. National Institutes of Health. | |||||
| 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 800011860) | |||||
| REF 4 | Clinical pipeline report, company report or official report of Amgen (2009). | |||||
| REF 5 | ClinicalTrials.gov (NCT00508625) Amgen. Report of Amgen. July 2007. | |||||
| REF 6 | 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: 1879). | |||||
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