Target Information
Target General Information | Top | |||||
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Target ID |
T29960
(Former ID: TTDR00688)
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Target Name |
Wilms tumor protein (WT1)
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Synonyms |
Wilms' tumour 1 protein; WT33; WT1 protein
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Gene Name |
WT1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 4 Target-related Diseases | + | ||||
1 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
2 | Leukaemia [ICD-11: 2A60-2B33] | |||||
3 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
4 | Lung cancer [ICD-11: 2C25] | |||||
Function |
Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has lower affinity for DNA, and can bind RNA. Transcription factor that plays an important role in cellular development and cell survival.
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BioChemical Class |
EGR C2H2-type zinc-finger
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UniProt ID | ||||||
Sequence |
MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAP
PPPPPPPPHSFIKQEPSWGGAEPHEEQCLSAFTVHFSGQFTGTAGACRYGPFGPPPPSQA SSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQ MNLGATLKGVAAGSSSSVKWTEGQSNHSTGYESDNHTTPILCGAQYRIHTHGVFRGIQDV RRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDC ERRFSRSDQLKRHQRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSCRWPS CQKKFARSDELVRHHNMHQRNMTKLQLAL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T28V82 |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
1 | Combined PR1/WT1 vaccine | Drug Info | Phase 2 | Myeloid leukaemia | [2] | |
2 | FPI-01 | Drug Info | Phase 2 | Acute myeloid leukaemia | [3] | |
3 | WT1 peptide vaccine | Drug Info | Phase 2 | leukaemia | [4] | |
4 | WT1-targeted autologous dendritic cell vaccine | Drug Info | Phase 2 | Acute myeloid leukaemia | [1] | |
5 | WT-4869 | Drug Info | Phase 1/2 | leukaemia | [5] | |
6 | GSK-2130579A | Drug Info | Phase 1 | Acute myeloid leukaemia | [6] | |
7 | INNO-305 | Drug Info | Phase 1 | Lung cancer | [7] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | WT-4869 | Drug Info | [11] | |||
2 | INNO-305 | Drug Info | [13] |
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 | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 4.27E-04 |
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Closeness centrality | 2.31E-01 | Radiality | 1.41E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 6.52E+01 | Topological coefficient | 2.01E-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-regulating Transcription Factors |
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 | Transcriptional misregulation in cancer | |||||
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | FSH Signaling Pathway | |||||
2 | IL5 Signaling Pathway | |||||
PID Pathway | [+] 2 PID Pathways | + | ||||
1 | p73 transcription factor network | |||||
2 | Regulation of Telomerase | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Primary Focal Segmental Glomerulosclerosis FSGS | |||||
2 | Integrated Pancreatic Cancer Pathway |
References | Top | |||||
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REF 1 | ClinicalTrials.gov (NCT01686334) Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission. U.S. National Institutes of Health. | |||||
REF 2 | Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies. Front Immunol. 2015 Feb 4;6:36. | |||||
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 800040574) | |||||
REF 4 | ClinicalTrials.gov (NCT01266083) Trial of a WT-1 Analog Peptide Vaccine in Patients With Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). U.S. National Institutes of Health. | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033385) | |||||
REF 6 | ClinicalTrials.gov (NCT01051063) Evaluation of a New Anti-cancer Immunotherapy in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy. U.S. National Institutes of Health. | |||||
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023753) | |||||
REF 8 | Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. | |||||
REF 9 | Clinical pipeline report, company report or official report of Formula Pharmaceuticals. | |||||
REF 10 | Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3beta sequence associated with remission in one patient is detectable in other vaccinated patients. Cancer ImmunolImmunother. 2012 Mar;61(3):313-22. | |||||
REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033385) | |||||
REF 12 | Spoilight on personalized medicine. A pharma matters report, Thomson Reuters, 2012. | |||||
REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023753) |
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