Target Information
| Target General Information | Top | |||||
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| Target ID |
T45612
(Former ID: TTDNC00398)
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| Target Name |
B7 homolog 3 (CD276)
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| Synonyms |
UNQ309/PRO352; PSEC0249; Costimulatory molecule; CD276 antigen; B7H3; B7-H3; 4IgB7H3; 4Ig-B7-H3
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| Gene Name |
CD276
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Adrenal cancer [ICD-11: 2D11] | |||||
| 2 | Brain cancer [ICD-11: 2A00] | |||||
| Function |
May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling. May participate in the regulation of T-cell-mediated immune response.
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSL
AQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSF TCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQD GQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQ RSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEG RDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY SKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIAL LVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T00YE6 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 11 Clinical Trial Drugs | + | ||||
| 1 | 131 I-omburtamab | Drug Info | Phase 2/3 | Neuroblastoma | [2] | |
| 2 | Omburtamab | Drug Info | Phase 2/3 | Neuroblastoma | [2] | |
| 3 | Omburtamab I-131 | Drug Info | Phase 2/3 | Neuroblastoma | [3] | |
| 4 | Enoblituzumab | Drug Info | Phase 2 | Solid tumour/cancer | [1], [4] | |
| 5 | TAK-280 | Drug Info | Phase 2 | Aggressive cancer | [5] | |
| 6 | DS-7300 | Drug Info | Phase 1/2 | Solid tumour/cancer | [6] | |
| 7 | MGC018 | Drug Info | Phase 1/2 | Solid tumour/cancer | [7] | |
| 8 | Omburtamab I-124 | Drug Info | Phase 1/2 | Glioma | [1], [8] | |
| 9 | 124I-8H9 | Drug Info | Phase 1 | Glioblastoma multiforme | [9] | |
| 10 | MGA271 | Drug Info | Phase 1 | Metastatic cancer | [10] | |
| 11 | MGD009 | Drug Info | Phase 1 | Solid tumour/cancer | [1], [4] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | 131 I-omburtamab | Drug Info | [11] | |||
| 2 | Omburtamab | Drug Info | [12] | |||
| 3 | Omburtamab I-131 | Drug Info | [1], [8] | |||
| 4 | Enoblituzumab | Drug Info | [4] | |||
| 5 | DS-7300 | Drug Info | [13] | |||
| 6 | Omburtamab I-124 | Drug Info | [1], [8] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | MGA271 | Drug Info | [16] | |||
| Immunomodulator | [+] 1 Immunomodulator drugs | + | ||||
| 1 | MGD009 | Drug Info | [4] | |||
| 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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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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| Cell adhesion molecules | hsa04514 | 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 | 2.03E-04 |
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| Closeness centrality | 2.00E-01 | Radiality | 1.35E+01 | Clustering coefficient | 3.33E-01 |
| Neighborhood connectivity | 1.73E+01 | Topological coefficient | 3.27E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Cell adhesion molecules (CAMs) | |||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | ClinicalTrials.gov (NCT03275402) 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT03275402) 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | ClinicalTrials.gov (NCT05220098) A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer. U.S.National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT04145622) Study of DS-7300a in Participants With Advanced Solid Malignant Tumors. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT03729596) MGC018 With or Without MGA012 in Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | ClinicalTrials.gov (NCT01099644) Intraperitoneal Radioimmunotherapy With 131I-8H9 for Patients With Desmoplastic Small Round Cell Tumors and Other Solid Tumors Involving the Peritoneum. U.S. NationalInstitutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT01918930) Tissue Procurement Substudy for Participants in Study CP-MGA271-01. U.S. National Institutes of Health. | |||||
| REF 11 | IntraOmmaya compartmental radioimmunotherapy using 131 I-omburtamab-pharmacokinetic modeling to optimize therapeutic index. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1166-1177. | |||||
| REF 12 | Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy. Cancer Immunol Immunother. 2021 Feb 3. | |||||
| REF 13 | Clinical pipeline report, company report or official report of Daiichi Sankyo. | |||||
| REF 14 | Clinical pipeline report, company report or official report of MacroGenics. | |||||
| REF 15 | National Cancer Institute Drug Dictionary (drug id 722029). | |||||
| REF 16 | T Cell Coinhibition and Immunotherapy in Human Breast Cancer. Discov Med. 2012 October; 14(77): 229-236. | |||||
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