Target Information
Target General Information | Top | |||||
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Target ID |
T93923
(Former ID: TTDNC00406)
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Target Name |
Co-stimulatory molecule 4-1BB (CD137)
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Synonyms |
Tumor necrosis factor receptor superfamily member 9; T-cell antigen ILA; T-cell antigen 4-1BB homolog; ILA; CDw137; 4-1BB ligand receptor
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Gene Name |
TNFRSF9
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 8 Target-related Diseases | + | ||||
1 | Melanoma [ICD-11: 2C30] | |||||
2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
3 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
4 | B-cell lymphoma [ICD-11: 2A86] | |||||
5 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
6 | Non-small-cell lung cancer [ICD-11: 2C25] | |||||
7 | Lymphoma [ICD-11: 2A80-2A86] | |||||
8 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
Function |
Possibly active during T cell activation. Receptor for TNFSF9/4-1BBL.
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BioChemical Class |
Cytokine receptor
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UniProt ID | ||||||
Sequence |
MGNSCYNIVATLLLVLNFERTRSLQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQR
TCDICRQCKGVFRTRKECSSTSNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDC CFGTFNDQKRGICRPWTNCSLDGKSVLVNGTKERDVVCGPSPADLSPGASSVTPPAPARE PGHSPQIISFFLALTSTALLFLLFFLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDG CSCRFPEEEEGGCEL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T72U9G |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 20 Clinical Trial Drugs | + | ||||
1 | Anti-CD137 | Drug Info | Phase 2 | Solid tumour/cancer | [2] | |
2 | Urelumab | Drug Info | Phase 2 | Solid tumour/cancer | [3], [4] | |
3 | ADG106 | Drug Info | Phase 1/2 | Non-hodgkin lymphoma | [5] | |
4 | CD137 CAR-T Cell | Drug Info | Phase 1/2 | Acute lymphoblastic leukaemia | [6] | |
5 | MG7-CART | Drug Info | Phase 1/2 | Acute myeloid leukaemia | [7] | |
6 | NM21-1480 | Drug Info | Phase 1/2 | Advanced solid tumour | [8] | |
7 | AGEN2373 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
8 | AMG 506 | Drug Info | Phase 1 | Solid tumour/cancer | [10] | |
9 | CD28 and CD137 CAR-T Cells | Drug Info | Phase 1 | Acute lymphoblastic leukaemia | [11] | |
10 | CTX-471 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
11 | GEN1042 | Drug Info | Phase 1 | Solid tumour/cancer | [13] | |
12 | GEN1046 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
13 | INBRX-105 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
14 | LVGN6051 | Drug Info | Phase 1 | Solid tumour/cancer | [16] | |
15 | MCLA-145 | Drug Info | Phase 1 | Lymphoma | [17] | |
16 | PF-05082566 | Drug Info | Phase 1 | Non-hodgkin lymphoma | [18] | |
17 | RG6076 | Drug Info | Phase 1 | Hematologic tumour | [19] | |
18 | RG6524 | Drug Info | Phase 1 | Aggressive cancer | [20] | |
19 | RG7827 | Drug Info | Phase 1 | Solid tumour/cancer | [19] | |
20 | Utomilumab | Drug Info | Phase 1 | Solid tumour/cancer | [21] | |
Mode of Action | [+] 6 Modes of Action | + | ||||
Agonist | [+] 8 Agonist drugs | + | ||||
1 | Urelumab | Drug Info | [3] | |||
2 | CTX-471 | Drug Info | [26] | |||
3 | GEN1042 | Drug Info | [27] | |||
4 | GEN1046 | Drug Info | [27] | |||
5 | INBRX-105 | Drug Info | [28] | |||
6 | MCLA-145 | Drug Info | [30] | |||
7 | RG7827 | Drug Info | [19] | |||
8 | Utomilumab | Drug Info | [32] | |||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | ADG106 | Drug Info | [22] | |||
2 | AMG 506 | Drug Info | [25] | |||
CAR-T-Cell-Therapy | [+] 2 CAR-T-Cell-Therapy drugs | + | ||||
1 | CD137 CAR-T Cell | Drug Info | [6] | |||
2 | MG7-CART | Drug Info | [7] | |||
Modulator | [+] 3 Modulator drugs | + | ||||
1 | NM21-1480 | Drug Info | [23] | |||
2 | PF-05082566 | Drug Info | [31] | |||
3 | HG-1051 | Drug Info | [1] | |||
Activator | [+] 2 Activator drugs | + | ||||
1 | AGEN2373 | Drug Info | [24] | |||
2 | LVGN6051 | Drug Info | [29] | |||
CAR-T-Cell-Therapy(Dual specific) | [+] 1 CAR-T-Cell-Therapy(Dual specific) drugs | + | ||||
1 | CD28 and CD137 CAR-T Cells | Drug Info | [11] |
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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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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Activation-inducible TNFR family receptor (TNFRSF18) | 30.168 (54/179) | 2.06E-10 |
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 |
Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.67E-05 |
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Closeness centrality | 2.04E-01 | Radiality | 1.36E+01 | Clustering coefficient | 1.67E-01 |
Neighborhood connectivity | 3.03E+01 | Topological coefficient | 3.04E-01 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Cytokine-cytokine receptor interaction | |||||
NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | TCR Signaling Pathway | |||||
PID Pathway | [+] 2 PID Pathways | + | ||||
1 | Downstream signaling in naï | |||||
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WikiPathways | [+] 1 WikiPathways | + | ||||
1 | TCR Signaling Pathway |
References | Top | |||||
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REF 1 | 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: 1878). | |||||
REF 2 | ClinicalTrials.gov (NCT00612664) Phase II, 2nd Line Melanoma - RAND Monotherapy. U.S. National Institutes of Health. | |||||
REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 5 | ClinicalTrials.gov (NCT04775680) Study of ADG106 In Combination With PD-1 Antibody In Advanced or Metastatic Solid Tumors and/or Non Hodgkin Lymphoma. U.S. National Institutes of Health. | |||||
REF 6 | ClinicalTrials.gov (NCT02965092) CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies | |||||
REF 7 | ClinicalTrials.gov (NCT02862704) A Study of MG7 Redirected Autologous T Cells for Advanced MG7 Positive Liver Metastases(MG7-CART) | |||||
REF 8 | ClinicalTrials.gov (NCT04442126) A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 9 | ClinicalTrials.gov (NCT04121676) Anti-CD137 Monoclonal Antibody in Patients With Advanced Cancer. U.S. National Institutes of Health. | |||||
REF 10 | ClinicalTrials.gov (NCT04049903) Study to Investigate the Safety, Blood Levels and Activity of MP0310 (AMG 506) in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 11 | ClinicalTrials.gov (NCT02186860) Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With Acute Lymphoblastic Leukemia | |||||
REF 12 | ClinicalTrials.gov (NCT03881488) Study of CTX-471 in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies. U.S. National Institutes of Health. | |||||
REF 13 | ClinicalTrials.gov (NCT04083599) GEN1042 Safety Trial in Subjects With Malignant Solid Tumors. U.S. National Institutes of Health. | |||||
REF 14 | ClinicalTrials.gov (NCT03917381) GEN1046 Safety Trial in Patients With Malignant Solid Tumors. U.S. National Institutes of Health. | |||||
REF 15 | ClinicalTrials.gov (NCT03809624) Study of INBRX-105 in Patients With Solid Tumors (PDL1x41BB). U.S. National Institutes of Health. | |||||
REF 16 | ClinicalTrials.gov (NCT04130542) Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy. U.S. National Institutes of Health. | |||||
REF 17 | ClinicalTrials.gov (NCT03922204) A Study of Bispecific Antibody MCLA-145 in Patients With Advanced or Metastatic Malignancies. U.S. National Institutes of Health. | |||||
REF 18 | ClinicalTrials.gov (NCT02179918) A Study Of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036). U.S. National Institutes of Health. | |||||
REF 19 | Clinical pipeline report, company report or official report of Roche. | |||||
REF 20 | Clinical pipeline report, company report or official report of Roche | |||||
REF 21 | ClinicalTrials.gov (NCT01307267) A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab. U.S. National Institutes of Health. | |||||
REF 22 | Clinical pipeline report, company report or official report of Adagene. | |||||
REF 23 | Clinical pipeline report, company report or official report of Numab Therapeutics. | |||||
REF 24 | Clinical pipeline report, company report or official report of Agenus. | |||||
REF 25 | Clinical pipeline report, company report or official report of Amgen. | |||||
REF 26 | Clinical pipeline report, company report or official report of Compass Therapeutics. | |||||
REF 27 | Clinical pipeline report, company report or official report of Genmab. | |||||
REF 28 | Clinical pipeline report, company report or official report of Inhibrx. | |||||
REF 29 | Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcR affinity. Nat Commun. 2019 May 20;10(1):2141. | |||||
REF 30 | Clinical pipeline report, company report or official report of Merus. | |||||
REF 31 | Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother. 2012 Oct;61(10):1721-33. | |||||
REF 32 | First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 + Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. |
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