Target Information
Target General Information | Top | |||||
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Target ID |
T87108
(Former ID: TTDNC00477)
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Target Name |
Mesothelin (MSLN)
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Synonyms |
Prepromegakaryocytepotentiating factor; Pre-pro-megakaryocyte-potentiating factor; Mesothelin, cleaved form; MPF; CAK1 antigen
Click to Show/Hide
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Gene Name |
MSLN
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 18 Target-related Diseases | + | ||||
1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
2 | Cervical cancer [ICD-11: 2C77] | |||||
3 | Liver cancer [ICD-11: 2C12] | |||||
4 | Lung cancer [ICD-11: 2C25] | |||||
5 | Non-small-cell lung cancer [ICD-11: 2C25] | |||||
6 | Ovarian cancer [ICD-11: 2C73] | |||||
7 | Peritoneal cancer [ICD-11: 2C51] | |||||
8 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
9 | Stomach cancer [ICD-11: 2B72] | |||||
10 | Endometrial cancer [ICD-11: 2C76] | |||||
11 | Fallopian tube cancer [ICD-11: 2C74] | |||||
12 | Lymphatic vessel/lymph nodes disorder [ICD-11: BD9Z] | |||||
13 | Mesothelial tumour [ICD-11: 2F10] | |||||
14 | Mesothelin positive tumour [ICD-11: 2C51-2F10] | |||||
15 | Metastatic malignant neoplasm [ICD-11: 2D50-2E09] | |||||
16 | Metastatic pleura neoplasm [ICD-11: 2D72] | |||||
17 | Pleural mesothelioma [ICD-11: 2C26] | |||||
18 | Pancreatic cancer [ICD-11: 2C10] | |||||
Function |
Membrane-anchored forms may play a role in cellular adhesion.
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UniProt ID | ||||||
Sequence |
MALPTARPLLGSCGTPALGSLLFLLFSLGWVQPSRTLAGETGQEAAPLDGVLANPPNISS
LSPRQLLGFPCAEVSGLSTERVRELAVALAQKNVKLSTEQLRCLAHRLSEPPEDLDALPL DLLLFLNPDAFSGPQACTRFFSRITKANVDLLPRGAPERQRLLPAALACWGVRGSLLSEA DVRALGGLACDLPGRFVAESAEVLLPRLVSCPGPLDQDQQEAARAALQGGGPPYGPPSTW SVSTMDALRGLLPVLGQPIIRSIPQGIVAAWRQRSSRDPSWRQPERTILRPRFRREVEKT ACPSGKKAREIDESLIFYKKWELEACVDAALLATQMDRVNAIPFTYEQLDVLKHKLDELY PQGYPESVIQHLGYLFLKMSPEDIRKWNVTSLETLKALLEVNKGHEMSPQAPRRPLPQVA TLIDRFVKGRGQLDKDTLDTLTAFYPGYLCSLSPEELSSVPPSSIWAVRPQDLDTCDPRQ LDVLYPKARLAFQNMNGSEYFVKIQSFLGGAPTEDLKALSQQNVSMDLATFMKLRTDAVL PLTVAEVQKLLGPHVEGLKAEERHRPVRDWILRQRQDDLDTLGLGLQGGIPNGYLVLDLS MQEALSGTPCLLGPGPVLTVLALLLASTLA 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) | [+] 30 Clinical Trial Drugs | + | ||||
1 | CRS-207 | Drug Info | Phase 2 | Pancreatic cancer | [2] | |
2 | MORAb-009 | Drug Info | Phase 2 | Mesothelioma | [3], [4] | |
3 | Anti-mesothelin CAR transduced PBL | Drug Info | Phase 1/2 | Cervical cancer | [5] | |
4 | Anti-Mesothelin CAR-T cells | Drug Info | Phase 1/2 | Gastric adenocarcinoma | [6] | |
5 | CAR-T cells targeting Mesothelin | Drug Info | Phase 1/2 | Cervical cancer | [7] | |
6 | CAR-T cells targeting mesothelin | Drug Info | Phase 1/2 | Pancreatic cancer | [8] | |
7 | HPN536 | Drug Info | Phase 1/2 | Solid tumour/cancer | [9] | |
8 | TC-210 | Drug Info | Phase 1/2 | Ovarian cancer | [10] | |
9 | TC-510 | Drug Info | Phase 1/2 | Breast cancer | [11] | |
10 | 227Th-labelled MSLN-TTC | Drug Info | Phase 1 | Epithelioid mesothelioma | [12] | |
11 | Anti-meso-CAR T cells | Drug Info | Phase 1 | Mesothelin Positive tumour | [13] | |
12 | Anti-meso-CAR vector transduced T cells | Drug Info | Phase 1 | Endometrial cancer | [13] | |
13 | Anti-mesothelin CAR T Cells | Drug Info | Phase 1 | Tumour | [14] | |
14 | Anti-Mesothelin CAR-T cells | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
15 | ATA2271 | Drug Info | Phase 1 | Mesothelioma | [16] | |
16 | Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1 | Drug Info | Phase 1 | Pancreatic cancer | [17] | |
17 | BAY 94-9343 | Drug Info | Phase 1 | Solid tumour/cancer | [18] | |
18 | CAR-T Cells targeting Mesothelin | Drug Info | Phase 1 | Pancreatic cancer | [19] | |
19 | CAR-T cells targeting Mesothelin | Drug Info | Phase 1 | Solid tumour/cancer | [20] | |
20 | CART-meso cells | Drug Info | Phase 1 | Pancreatic cancer | [21] | |
21 | CART-meso-19 T cells | Drug Info | Phase 1 | Pancreatic cancer | [22] | |
22 | CARTmeso/19 | Drug Info | Phase 1 | Pancreatic cancer | [23] | |
23 | Hu-CART meso cells | Drug Info | Phase 1 | Fallopian tube cancer | [24] | |
24 | HuCART-meso cells | Drug Info | Phase 1 | Lymphatic disease | [25] | |
25 | ICasp9M28z T cell | Drug Info | Phase 1 | Lung cancer | [26] | |
26 | MCY-M11 | Drug Info | Phase 1 | Ovarian cancer | [27] | |
27 | Meso-CART | Drug Info | Phase 1 | Pancreatic cancer | [28] | |
28 | Mesothelin-targeted T cells | Drug Info | Phase 1 | Breast cancer | [29] | |
29 | RG7882 | Drug Info | Phase 1 | Ovarian cancer | [30] | |
30 | CART-meso cells | Drug Info | Clinical trial | Pancreatic cancer | [31] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | SS1(dsFv)-PE38 | Drug Info | Discontinued in Phase 1 | Solid tumour/cancer | [32] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | ATA3271 | Drug Info | Preclinical | Solid tumour/cancer | [33] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
CAR-T-Cell-Therapy | [+] 18 CAR-T-Cell-Therapy drugs | + | ||||
1 | Anti-mesothelin CAR transduced PBL | Drug Info | [5] | |||
2 | Anti-Mesothelin CAR-T cells | Drug Info | [6] | |||
3 | CAR-T cells targeting Mesothelin | Drug Info | [7], [36] | |||
4 | CAR-T cells targeting mesothelin | Drug Info | [8] | |||
5 | Anti-meso-CAR T cells | Drug Info | [13] | |||
6 | Anti-meso-CAR vector transduced T cells | Drug Info | [13] | |||
7 | Anti-mesothelin CAR T Cells | Drug Info | [14] | |||
8 | Anti-Mesothelin CAR-T cells | Drug Info | [15] | |||
9 | Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1 | Drug Info | [17] | |||
10 | CAR-T Cells targeting Mesothelin | Drug Info | [19] | |||
11 | CAR-T cells targeting Mesothelin | Drug Info | [20] | |||
12 | CART-meso cells | Drug Info | [21] | |||
13 | Hu-CART meso cells | Drug Info | [24] | |||
14 | HuCART-meso cells | Drug Info | [25] | |||
15 | ICasp9M28z T cell | Drug Info | [26] | |||
16 | Meso-CART | Drug Info | [28] | |||
17 | Mesothelin-targeted T cells | Drug Info | [29] | |||
18 | CART-meso cells | Drug Info | [31] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | BAY 94-9343 | Drug Info | [41] | |||
CAR-T-Cell-Therapy(Dual specific) | [+] 2 CAR-T-Cell-Therapy(Dual specific) drugs | + | ||||
1 | CART-meso-19 T cells | Drug Info | [22] | |||
2 | CARTmeso/19 | Drug Info | [23] |
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).
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 | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.73E-01 | Radiality | 1.28E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 1.70E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
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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NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | TCR Signaling Pathway |
References | Top | |||||
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REF 1 | Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res. 2014 Dec 1;20(23):5927-36. | |||||
REF 2 | ClinicalTrials.gov (NCT02243371) GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab. U.S. National Institutes of Health. | |||||
REF 3 | 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: 7750). | |||||
REF 4 | ClinicalTrials.gov (NCT00570713) An Efficacy Study of MORAb-009 in Subjects With Pancreatic Cancer. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT01583686) CAR T Cell Receptor Immunotherapy Targeting Mesothelin for Patients With Metastatic Cancer | |||||
REF 6 | ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies | |||||
REF 7 | ClinicalTrials.gov (NCT03356795) Intervention of CAR-T Against Cervical Cancer | |||||
REF 8 | ClinicalTrials.gov (NCT02959151) A Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy | |||||
REF 9 | ClinicalTrials.gov (NCT03872206) Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression. U.S. National Institutes of Health. | |||||
REF 10 | ClinicalTrials.gov (NCT03907852) Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer. U.S. National Institutes of Health. | |||||
REF 11 | ClinicalTrials.gov (NCT05451849) A Phase 1/2 Single Arm Open-Label Clinical Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer. U.S.National Institutes of Health. | |||||
REF 12 | ClinicalTrials.gov (NCT03507452) First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin. U.S. National Institutes of Health. | |||||
REF 13 | ClinicalTrials.gov (NCT02580747) Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART-meso | |||||
REF 14 | ClinicalTrials.gov (NCT02930993) Anti-mesothelin CAR T Cells for Patients With Recurrent or Metastatic Malignant Tumors | |||||
REF 15 | ClinicalTrials.gov (NCT03545815) Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors. | |||||
REF 16 | Clinical pipeline report, company report or official report of Atara Biotherapeutics. | |||||
REF 17 | ClinicalTrials.gov (NCT01897415) Autologous Redirected RNA Meso CAR T Cells for Pancreatic Cancer | |||||
REF 18 | ClinicalTrials.gov (NCT01439152) Phase I Study to Determine the Maximum Tolerable Dose of BAY94-9343 in Patients With Advanced Solid Tumors.. U.S. National Institutes of Health. | |||||
REF 19 | ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer. | |||||
REF 20 | ClinicalTrials.gov (NCT03198052) HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T Cells Immunotherapy Against Cancers | |||||
REF 21 | ClinicalTrials.gov (NCT02159716) CART-meso in Mesothelin Expressing Cancers | |||||
REF 22 | ClinicalTrials.gov (NCT02465983) Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer | |||||
REF 23 | ClinicalTrials.gov (NCT03497819) Autologous CARTmeso/19 Against Pancreatic Cancer | |||||
REF 24 | ClinicalTrials.gov (NCT03054298) CAR T Cells in Mesothelin Expressing Cancers | |||||
REF 25 | ClinicalTrials.gov (NCT03323944) CAR T Cell Immunotherapy for Pancreatic Cancer | |||||
REF 26 | ClinicalTrials.gov (NCT02414269) Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin | |||||
REF 27 | ClinicalTrials.gov (NCT03608618) Intraperitoneal MCY-M11 (Mesothelin-targeting CAR) for Treatment of Advanced Ovarian Cancer and Peritoneal Mesothelioma. U.S. National Institutes of Health. | |||||
REF 28 | ClinicalTrials.gov (NCT02706782) A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma | |||||
REF 29 | ClinicalTrials.gov (NCT02792114) T-Cell Therapy for Advanced Breast Cancer | |||||
REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028960) | |||||
REF 31 | ClinicalTrials.gov (NCT03638193) Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer | |||||
REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012262) | |||||
REF 33 | Clinical pipeline report, company report or official report of Atara Biotherapeutics. | |||||
REF 34 | Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. | |||||
REF 35 | National Cancer Institute Drug Dictionary (drug id 543500). | |||||
REF 36 | ClinicalTrials.gov (NCT03356808) Antigen-specific T Cells Against Lung Cancer | |||||
REF 37 | Clinical pipeline report, company report or official report of Harpoon Therapeutics. | |||||
REF 38 | Clinical pipeline report, company report or official report of TCR2 Therapeutics. | |||||
REF 39 | Clinical pipeline report, company report or official report of TCR2 Therapeutics | |||||
REF 40 | Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers. Clin Cancer Res. 2019 Aug 1;25(15):4723-4734. | |||||
REF 41 | National Cancer Institute Drug Dictionary (drug id 712853). | |||||
REF 42 | Clinical pipeline report, company report or official report of MaxCyte. | |||||
REF 43 | Molecular Imaging As a Tool for Drug Development and Trial Design. JCO July 13, 2015 JCO.2015.61.6425 | |||||
REF 44 | Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008 Jan;44(1):46-53. |
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