Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ8UT4)

• DTT Name: Wilms tumor protein (WT1)
• Synonyms: Wilms' tumour 1 protein; WT33; WT1 protein
• Gene Name: WT1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: EGR C2H2-type zinc-finger
• UniProt ID: WT1_HUMAN
• TTD ID: T29960
• Sequence:
  MGSDVRDLNALLPAVPSLGGGGGCALPVSGAAQWAPVLDFAPPGASAYGSLGGPAPPPAP
  PPPPPPPPHSFIKQEPSWGGAEPHEEQCLSAFTVHFSGQFTGTAGACRYGPFGPPPPSQA
  SSGQARMFPNAPYLPSCLESQPAIRNQGYSTVTFDGTPSYGHTPSHHAAQFPNHSFKHED
  PMGQQGSLGEQQYSVPPPVYGCHTPTDSCTGSQALLLRTPYSSDNLYQMTSQLECMTWNQ
  MNLGATLKGVAAGSSSSVKWTEGQSNHSTGYESDNHTTPILCGAQYRIHTHGVFRGIQDV
  RRVPGVAPTLVRSASETSEKRPFMCAYPGCNKRYFKLSHLQMHSRKHTGEKPYQCDFKDC
  ERRFSRSDQLKRHQRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSCRWPS
  CQKKFARSDELVRHHNMHQRNMTKLQLAL
• 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.
• KEGG Pathway: Transcriptional misregulation in cancer (hsa05202)
• Reactome Pathway: Transcriptional regulation of testis differentiation (R-HSA-9690406)

Molecular Interaction Atlas (MIA) of This DTT

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Combined PR1/WT1 vaccine	DMGCTX5	Myeloid leukaemia	2B33.1	Phase 2	[2]
FPI-01	DMXOTMP	Acute myeloid leukaemia	2A60	Phase 2	[3]
WT1 peptide vaccine	DMZ67Q0	leukaemia	2A60-2B33	Phase 2	[4]
WT1-targeted autologous dendritic cell vaccine	DMNFZYE	Acute myeloid leukaemia	2A60	Phase 2	[1]
WT-4869	DM3FIMD	leukaemia	2A60-2B33	Phase 1/2	[5]
GSK-2130579A	DMRXW9P	Acute myeloid leukaemia	2A60	Phase 1	[6]
INNO-305	DMG6S8U	Acute myeloid leukaemia	2A60	Phase 1	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	5.12E-79	1.54	7.84

References

• [1] ClinicalTrials.gov (NCT01686334) Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission. U.S. National Institutes of Health.
• [2] 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.
• [3] Clinical pipeline report, company report or official report of Formula Pharmaceuticals.
• [4] 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.
• [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)
• [6] Spoilight on personalized medicine. A pharma matters report, Thomson Reuters, 2012.
• [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)