Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTXDIK2)

• DTT Name: Notch-4 receptor (NOTCH4)
• Synonyms: hNotch4; Notch 4; Neurogenic locus notch homolog protein 4; INT3
• Gene Name: NOTCH4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Notch protein
• UniProt ID: NOTC4_HUMAN
• TTD ID: T49453
• Sequence:
  MQPPSLLLLLLLLLLLCVSVVRPRGLLCGSFPEPCANGGTCLSLSLGQGTCQCAPGFLGE
  TCQFPDPCQNAQLCQNGGSCQALLPAPLGLPSSPSPLTPSFLCTCLPGFTGERCQAKLED
  PCPPSFCSKRGRCHIQASGRPQCSCMPGWTGEQCQLRDFCSANPCVNGGVCLATYPQIQC
  HCPPGFEGHACERDVNECFQDPGPCPKGTSCHNTLGSFQCLCPVGQEGPRCELRAGPCPP
  RGCSNGGTCQLMPEKDSTFHLCLCPPGFIGPDCEVNPDNCVSHQCQNGGTCQDGLDTYTC
  LCPETWTGWDCSEDVDECETQGPPHCRNGGTCQNSAGSFHCVCVSGWGGTSCEENLDDCI
  AATCAPGSTCIDRVGSFSCLCPPGRTGLLCHLEDMCLSQPCHGDAQCSTNPLTGSTLCLC
  QPGYSGPTCHQDLDECLMAQQGPSPCEHGGSCLNTPGSFNCLCPPGYTGSRCEADHNECL
  SQPCHPGSTCLDLLATFHCLCPPGLEGQLCEVETNECASAPCLNHADCHDLLNGFQCICL
  PGFSGTRCEEDIDECRSSPCANGGQCQDQPGAFHCKCLPGFEGPRCQTEVDECLSDPCPV
  GASCLDLPGAFFCLCPSGFTGQLCEVPLCAPNLCQPKQICKDQKDKANCLCPDGSPGCAP
  PEDNCTCHHGHCQRSSCVCDVGWTGPECEAELGGCISAPCAHGGTCYPQPSGYNCTCPTG
  YTGPTCSEEMTACHSGPCLNGGSCNPSPGGYYCTCPPSHTGPQCQTSTDYCVSAPCFNGG
  TCVNRPGTFSCLCAMGFQGPRCEGKLRPSCADSPCRNRATCQDSPQGPRCLCPTGYTGGS
  CQTLMDLCAQKPCPRNSHCLQTGPSFHCLCLQGWTGPLCNLPLSSCQKAALSQGIDVSSL
  CHNGGLCVDSGPSYFCHCPPGFQGSLCQDHVNPCESRPCQNGATCMAQPSGYLCQCAPGY
  DGQNCSKELDACQSQPCHNHGTCTPKPGGFHCACPPGFVGLRCEGDVDECLDQPCHPTGT
  AACHSLANAFYCQCLPGHTGQWCEVEIDPCHSQPCFHGGTCEATAGSPLGFICHCPKGFE
  GPTCSHRAPSCGFHHCHHGGLCLPSPKPGFPPRCACLSGYGGPDCLTPPAPKGCGPPSPC
  LYNGSCSETTGLGGPGFRCSCPHSSPGPRCQKPGAKGCEGRSGDGACDAGCSGPGGNWDG
  GDCSLGVPDPWKGCPSHSRCWLLFRDGQCHPQCDSEECLFDGYDCETPPACTPAYDQYCH
  DHFHNGHCEKGCNTAECGWDGGDCRPEDGDPEWGPSLALLVVLSPPALDQQLFALARVLS
  LTLRVGLWVRKDRDGRDMVYPYPGARAEEKLGGTRDPTYQERAAPQTQPLGKETDSLSAG
  FVVVMGVDLSRCGPDHPASRCPWDPGLLLRFLAAMAAVGALEPLLPGPLLAVHPHAGTAP
  PANQLPWPVLCSPVAGVILLALGALLVLQLIRRRRREHGALWLPPGFTRRPRTQSAPHRR
  RPPLGEDSIGLKALKPKAEVDEDGVVMCSGPEEGEEVGQAEETGPPSTCQLWSLSGGCGA
  LPQAAMLTPPQESEMEAPDLDTRGPDGVTPLMSAVCCGEVQSGTFQGAWLGCPEPWEPLL
  DGGACPQAHTVGTGETPLHLAARFSRPTAARRLLEAGANPNQPDRAGRTPLHAAVAADAR
  EVCQLLLRSRQTAVDARTEDGTTPLMLAARLAVEDLVEELIAAQADVGARDKWGKTALHW
  AAAVNNARAARSLLQAGADKDAQDNREQTPLFLAAREGAVEVAQLLLGLGAARELRDQAG
  LAPADVAHQRNHWDLLTLLEGAGPPEARHKATPGREAGPFPRARTVSVSVPPHGGGALPR
  CRTLSAGAGPRGGGACLQARTWSVDLAARGGGAYSHCRSLSGVGAGGGPTPRGRRFSAGM
  RGPRPNPAIMRGRYGVAAGRGGRVSTDDWPCDWVALGACGSASNIPIPPPCLTPSPERGS
  PQLDCGPPALQEMPINQGGEGKK
• Function: Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May regulate branching morphogenesis in the developing vascular system. Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination.
• KEGG Pathway:
  Dorso-ventral axis formation (hsa04320)
  Notch signaling pathway (hsa04330)
  Thyroid hormone signaling pathway (hsa04919)
  Prion diseases (hsa05020)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)
  NOTCH2 intracellular domain regulates transcription (R-HSA-2197563)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 t(7 (R-HSA-2660826)
  Constitutive Signaling by NOTCH1 HD Domain Mutants (R-HSA-2691232)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  Notch-HLH transcription pathway (R-HSA-350054)
  M1580_K2555) Translocation Mutant (9)(NOTCH1)
  Pre-NOTCH Processing in the Endoplasmic Reticulum (R-HSA-1912399)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY3039478	DMC5SAW	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]

References

• [1] J Clin Oncol 33, 2015 (suppl; abstr 2533).