Target Information
| Target General Information | Top | |||||
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| Target ID |
T47863
(Former ID: TTDR00765)
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| Target Name |
Tumor-associated calcium signal transducer 1 (EPCAM)
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| Synonyms |
hEGP314; TROP1; TACSTD1; Major gastrointestinal tumor-associated protein GA733-2; MIC18; M4S1; M1S2; KSA; KS 1/4 antigen; Gastrointestinal carcinoma antigen GA733; GA733-2; Epithelial glycoprotein 314; Epithelial glycoprotein; Epithelial cell surface antigen; Epithelial cell adhesion molecule; Ep-CAM; EGP314; EGP; Cell surface glycoprotein Trop-1; CD326; Adenocarcinoma-associated antigen
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| Gene Name |
EPCAM
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Bladder cancer [ICD-11: 2C94] | |||||
| 2 | Head and neck cancer [ICD-11: 2D42] | |||||
| Function |
Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection.
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| UniProt ID | ||||||
| Sequence |
MAPPQVLAFGLLLAAATATFAAAQEECVCENYKLAVNCFVNNNRQCQCTSVGAQNTVICS
KLAAKCLVMKAEMNGSKLGRRAKPEGALQNNDGLYDPDCDESGLFKAKQCNGTSMCWCVN TAGVRRTDKDTEITCSERVRTYWIIIELKHKAREKPYDSKSLRTALQKEITTRYQLDPKF ITSILYENNVITIDLVQNSSQKTQNDVDIADVAYYFEKDVKGESLFHSKKMDLTVNGEQL DLDPGQTLIYYVDEKAPEFSMQGLKAGVIAVIVVVVIAVVAGIVVLVISRKKRMAKYEKA EIKEMGEMHRELNA 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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| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | VB4-845 | Drug Info | Phase 2/3 | Head and neck cancer | [3] | |
| 2 | CAR-T Cells targeting EpCAM | Drug Info | Phase 1/2 | Colon cancer | [4] | |
| 3 | CAR-T cells recognizing EpCAM | Drug Info | Phase 1 | Melanoma | [6] | |
| 4 | CAR-T cells targeting EpCAM | Drug Info | Phase 1 | Metastatic cancer | [7] | |
| 5 | Citatuzumab bogatox | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| 6 | ING-1 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
| 7 | MT-110 | Drug Info | Phase 1 | Solid tumour/cancer | [10] | |
| 8 | EPCAM-targeted CAR-T cells | Drug Info | Clinical trial | Liver cancer | [11] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | IGN-101 | Drug Info | Discontinued in Phase 2 | Colorectal cancer | [12] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| CAR-T-Cell-Therapy | [+] 4 CAR-T-Cell-Therapy drugs | + | ||||
| 1 | CAR-T Cells targeting EpCAM | Drug Info | [4] | |||
| 2 | CAR-T cells recognizing EpCAM | Drug Info | [6] | |||
| 3 | CAR-T cells targeting EpCAM | Drug Info | [7] | |||
| 4 | EPCAM-targeted CAR-T cells | Drug Info | [11], [15] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Pyroglutamic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of extracellular part of human EpCAM | PDB:4MZV | ||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | Yes | [17] |
| PDB Sequence |
EECVCENYKL
34 AVNCFVNNNR44 QCQCTSVGAQ54 NTVICSKLAA64 KCLVMKAEMQ74 GSKLGRRAKP 84 EGALQNNDGL94 YDPDCDESGL104 FKAKQCQGTS114 TCWCVNTAGV124 RRTDKDTEIT 134 CSERVRTYWI144 IIELKHKARE154 KPYDSKSLRT164 ALQKEITTRY174 QLDPKFITSI 184 LYENNVITID194 LVQQSSQKTQ204 NDVDIADVAY214 YFEKDVKGES224 LFHSKKMDLT 234 VNGEQLDLDP244 GQTLIYYVDE254 KAPEFSMQGL264 KH
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| Ligand Name: Decyl-beta-D-maltopyranoside | Ligand Info | |||||
| Structure Description | Crystal structure of extracellular part of human EpCAM | PDB:4MZV | ||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | Yes | [17] |
| PDB Sequence |
EECVCENYKL
34 AVNCFVNNNR44 QCQCTSVGAQ54 NTVICSKLAA64 KCLVMKAEMQ74 GSKLGRRAKP 84 EGALQNNDGL94 YDPDCDESGL104 FKAKQCQGTS114 TCWCVNTAGV124 RRTDKDTEIT 134 CSERVRTYWI144 IIELKHKARE154 KPYDSKSLRT164 ALQKEITTRY174 QLDPKFITSI 184 LYENNVITID194 LVQQSSQKTQ204 NDVDIADVAY214 YFEKDVKGES224 LFHSKKMDLT 234 VNGEQLDLDP244 GQTLIYYVDE254 KAPEFSMQGL264 KH
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ILE146
3.605
LEU148
4.284
LEU166
3.801
GLU169
3.980
ILE170
3.719
ARG173
3.537
TYR174
3.500
ILE193
3.870
LEU195
4.479
VAL212
3.880
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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).
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
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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| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 3.74E-05 |
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| Closeness centrality | 2.24E-01 | Radiality | 1.39E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.06E+02 | Topological coefficient | 5.00E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | A bispecific EpCAM/CD133 targeted toxin is effective against carcinoma. Target Oncol. 2014 September; 9(3): 239-249. | |||||
| REF 2 | Clinical pipeline report, company report or official report of Sesen Bio. | |||||
| 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 800017525) | |||||
| REF 4 | ClinicalTrials.gov (NCT03013712) A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer | |||||
| REF 5 | Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608. | |||||
| REF 6 | ClinicalTrials.gov (NCT02915445) EpCAM CAR-T for Treatment of Nasopharyngeal Carcinoma and Breast Cancer | |||||
| REF 7 | ClinicalTrials.gov (NCT03563326) Intraperitoneal Infusion of EpCAM CAR-T Cell in Advanced Gastric Cancer With Peritoneal Metastasis (WCH-GC-CART) | |||||
| REF 8 | ClinicalTrials.gov (NCT00481936) Study of the Safety of VB6-845 in Patients With Advanced Solid Tumours of Epithelial Origin. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT00051675) Phase I Study of a Monoclonal Antibody for Treatment of Advanced Adenocarcinomas. U.S. National Institutes of Health. | |||||
| REF 10 | EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012 Jan 15;18(2):465-74. | |||||
| REF 11 | ClinicalTrials.gov (NCT02729493) Study Evaluating the Efficacy and Safety With CAR-T for Liver Cancer | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013809) | |||||
| REF 13 | Preclinical evaluation of VB6-845: an anti-EpCAM immunotoxin with reduced immunogenic potential. Cancer Biother Radiopharm. 2012 Nov;27(9):582-92. | |||||
| REF 14 | ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clin Cancer Res. 2004 Nov 15;10(22):7555-65. | |||||
| REF 15 | ClinicalTrials.gov (NCT02725125) Study Evaluating the Efficacy and Safety With CAR-T for Stomach Cancer | |||||
| REF 16 | Drug evaluation: IGN-101--an anti-EpCAM murine antibody vaccine for cancer. Curr Opin Mol Ther. 2006 Aug;8(4):358-65. | |||||
| REF 17 | Crystal structure and its bearing towards an understanding of key biological functions of EpCAM. Nat Commun. 2014 Aug 28;5:4764. | |||||
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