Target Information
Target General Information | Top | |||||
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Target ID |
T88023
(Former ID: TTDR00192)
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Target Name |
Lymphocyte activation antigen CD30 (TNFRSF8)
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Synonyms |
Tumor necrosis factor receptor superfamily member 8; KI-1 antigen; D1S166E; CD30L receptor; CD30
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Gene Name |
TNFRSF8
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hodgkin lymphoma [ICD-11: 2B30] | |||||
Function |
May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B. Receptor for TNFSF8/CD30L.
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UniProt ID | ||||||
Sequence |
MRVLLAALGLLFLGALRAFPQDRPFEDTCHGNPSHYYDKAVRRCCYRCPMGLFPTQQCPQ
RPTDCRKQCEPDYYLDEADRCTACVTCSRDDLVEKTPCAWNSSRVCECRPGMFCSTSAVN SCARCFFHSVCPAGMIVKFPGTAQKNTVCEPASPGVSPACASPENCKEPSSGTIPQAKPT PVSPATSSASTMPVRGGTRLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDC RKQCEPDYYLDEAGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARC VPYPICAAETVTKPQDMAEKDTTFEAPPLGTQPDCNPTPENGEAPASTSPTQSLLVDSQA SKTLPIPTSAPVALSSTGKPVLDAGPVLFWVILVLVVVVGSSAFLLCHRRACRKRIRQKL HLCYPVQTSQPKLELVDSRPRRSSTQLRSGASVTEPVAEERGLMSQPLMETCHSVGAAYL ESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGL AGPAEPELEEELEADHTPHYPEQETEPPLGSCSDVMLSVEEEGKEDPLPTAASGK Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Brentuximab vedotin | Drug Info | Approved | Hodgkin lymphoma | [2], [3], [4] | |
Clinical Trial Drug(s) | [+] 14 Clinical Trial Drugs | + | ||||
1 | CAR-T cells targeting CD30 | Drug Info | Phase 2 | Non-hodgkin lymphoma | [7] | |
2 | Iratumumab | Drug Info | Phase 2 | Lymphoma | [8] | |
3 | SGN-30 | Drug Info | Phase 2 | Solid tumour/cancer | [9] | |
4 | 4SCAR19 and 4SCAR30 | Drug Info | Phase 1/2 | B-cell lymphoma | [12] | |
5 | Anti-CD30 CAR T cells | Drug Info | Phase 1/2 | Lymphoma | [13] | |
6 | CAR.CD30 cells | Drug Info | Phase 1/2 | Immune System disease | [14], [15] | |
7 | CART30 | Drug Info | Phase 1/2 | Non-hodgkin lymphoma | [16] | |
8 | Anti-CD30 CAR-T cells | Drug Info | Phase 1 | leukaemia | [19] | |
9 | Anti-CD30-CAR T cells | Drug Info | Phase 1 | Hodgkin lymphoma | [20] | |
10 | ATLCAR.CD30 cells | Drug Info | Phase 1 | Immune System disease | [17] | |
11 | CAR CD30 T cells | Drug Info | Phase 1 | Non-hodgkin lymphoma | [21] | |
12 | CD30 CAR T Cells | Drug Info | Phase 1 | Non-hodgkin lymphoma | [22] | |
13 | ICAR30 T cells | Drug Info | Phase 1 | Anaplastic large cell lymphoma | [23] | |
14 | Xmab-2513 | Drug Info | Phase 1 | Lymphoma | [24] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | Brentuximab vedotin | Drug Info | [1] | |||
2 | VT-362 | Drug Info | [30] | |||
CAR-T-Cell-Therapy | [+] 10 CAR-T-Cell-Therapy drugs | + | ||||
1 | CAR-T cells targeting CD30 | Drug Info | [7] | |||
2 | Anti-CD30 CAR T cells | Drug Info | [13] | |||
3 | CAR.CD30 cells | Drug Info | [14], [15] | |||
4 | CART30 | Drug Info | [16] | |||
5 | Anti-CD30 CAR-T cells | Drug Info | [19] | |||
6 | Anti-CD30-CAR T cells | Drug Info | [20] | |||
7 | ATLCAR.CD30 cells | Drug Info | [17] | |||
8 | CAR CD30 T cells | Drug Info | [21] | |||
9 | CD30 CAR T Cells | Drug Info | [22] | |||
10 | ICAR30 T cells | Drug Info | [23] | |||
CAR-T-Cell-Therapy(Dual specific) | [+] 1 CAR-T-Cell-Therapy(Dual specific) drugs | + | ||||
1 | 4SCAR19 and 4SCAR30 | Drug Info | [12] |
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 |
Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 2.02E-04 |
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Closeness centrality | 2.02E-01 | Radiality | 1.35E+01 | Clustering coefficient | 5.00E-01 |
Neighborhood connectivity | 3.15E+01 | Topological coefficient | 3.72E-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 | [+] 2 NetPath Pathways | + | ||||
1 | Leptin Signaling Pathway | |||||
2 | TCR Signaling Pathway |
References | Top | |||||
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REF 1 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
REF 2 | 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. (Ligand id: 6772). | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 4 | ClinicalTrials.gov (NCT01990534) A Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT02321592) GHSG-AFM13 An Open-label, Multicenter Phase II Trial With AFM13 in Patients With Relapsed or Refractory Hodgkin Lymphoma. U.S. National Institutes of Health. | |||||
REF 6 | Clinical pipeline report, company report or official report of Tessa Therapeutics | |||||
REF 7 | ClinicalTrials.gov (NCT03196830) CAR-T for R/R B-NHL | |||||
REF 8 | ClinicalTrials.gov (NCT00284804) A Phase II Study of MDX-060 in Subjects With Relapsed or Refractory Hodgkin's Disease. U.S. National Institutes of Health. | |||||
REF 9 | ClinicalTrials.gov (NCT00099255) Study of SGN-30 (Anti-CD30 mAb) in Patients With Primary Cutaneous Anaplastic Large Cell Lymphoma. U.S. National Institutes of Health. | |||||
REF 10 | ClinicalTrials.gov (NCT03312205) CAR-T Cells for Relapsed or Refractory Haematopoietic and Lymphoid Malignancies | |||||
REF 11 | ClinicalTrials.gov (NCT02958410) A Clinical Research of CD30-Targeted CAR-T in Lymphocyte Malignancies | |||||
REF 12 | ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies | |||||
REF 13 | ClinicalTrials.gov (NCT02274584) CAR T Cells Targeting CD30 Positive Lymphomas (4SCAR30273) | |||||
REF 14 | ClinicalTrials.gov (NCT02663297) Administration of T Lymphocytes for Prevention of Relapse of Lymphomas | |||||
REF 15 | ClinicalTrials.gov (NCT02690545) Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL | |||||
REF 16 | ClinicalTrials.gov (NCT02259556) CD30-directed Chimeric Antigen Receptor T (CART30) Therapy in Relapsed and Refractory CD30 Positive Lymphomas | |||||
REF 17 | ClinicalTrials.gov (NCT03602157) Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and NHL | |||||
REF 18 | Clinical pipeline report, company report or official report of Seagen. | |||||
REF 19 | ClinicalTrials.gov (NCT03121625) CAR-T Therapy in Relapsed or Refractory Haematopoietic and Lymphoid Malignancies | |||||
REF 20 | ClinicalTrials.gov (NCT03049449) T Cells Expressing a Fully-Human Anti-CD30 Chimeric Antigen Receptor for Treating CD30-Expressing Lymphomas | |||||
REF 21 | ClinicalTrials.gov (NCT01316146) Administration of T Lymphocytes for Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (CART CD30) | |||||
REF 22 | ClinicalTrials.gov (NCT02917083) CD30 CAR T Cells, Relapsed CD30 Expressing Lymphoma (RELY-30) | |||||
REF 23 | ClinicalTrials.gov (NCT03383965) CD30 Targeted CAR-T in Treating CD30-Expressing Lymphomas | |||||
REF 24 | ClinicalTrials.gov (NCT00606645) Safety Study of XmAb2513 to Treat Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma. U.S. National Institutes of Health. | |||||
REF 25 | Utilizing CD30 expression as a rational target for therapy of lymphoma. J Hematol Oncol. 2012; 5(Suppl 1): A2. | |||||
REF 26 | The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002 Jul 1;62(13):3736-42. | |||||
REF 27 | Phase I study of an anti-CD30 Fc engineered humanized monoclonal antibody in Hodgkin lymphoma (HL) or anaplastic large cell lymphoma (ALCL) patients: Safety, pharmacokinetics (PK), immunogenicity, and efficacy. J Clin Oncol (Meeting Abstracts) May 2009 vol. 27 no. 15S 8531. | |||||
REF 28 | Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in severe combined immunodeficiency disease mice xenografted with human CD30+ anaplastic large-cell lymphoma. Blood. 1995 Apr15;85(8):2139-46. | |||||
REF 29 | Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma. Blood. 2002 Nov 1;100(9):3101-7. | |||||
REF 30 | 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: 1877). |
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