Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTV23LH)

• DTT Name: Delta-like protein 4 (DLL4)
• Synonyms: UNQ1895/PRO4341; Drosophila Delta homolog 4; Deltalike protein 4; Delta4
• Gene Name: DLL4
• DTT Type: Clinical trial target; [1]
• UniProt ID: DLL4_HUMAN
• TTD ID: T55273
• Sequence:
  MAAASRSASGWALLLLVALWQQRAAGSGVFQLQLQEFINERGVLASGRPCEPGCRTFFRV
  CLKHFQAVVSPGPCTFGTVSTPVLGTNSFAVRDDSSGGGRNPLQLPFNFTWPGTFSLIIE
  AWHAPGDDLRPEALPPDALISKIAIQGSLAVGQNWLLDEQTSTLTRLRYSYRVICSDNYY
  GDNCSRLCKKRNDHFGHYVCQPDGNLSCLPGWTGEYCQQPICLSGCHEQNGYCSKPAECL
  CRPGWQGRLCNECIPHNGCRHGTCSTPWQCTCDEGWGGLFCDQDLNYCTHHSPCKNGATC
  SNSGQRSYTCTCRPGYTGVDCELELSECDSNPCRNGGSCKDQEDGYHCLCPPGYYGLHCE
  HSTLSCADSPCFNGGSCRERNQGANYACECPPNFTGSNCEKKVDRCTSNPCANGGQCLNR
  GPSRMCRCRPGFTGTYCELHVSDCARNPCAHGGTCHDLENGLMCTCPAGFSGRRCEVRTS
  IDACASSPCFNRATCYTDLSTDTFVCNCPYGFVGSRCEFPVGLPPSFPWVAVSLGVGLAV
  LLVLLGMVAVAVRQLRLRRPDDGSREAMNNLSDFQKDNLIPAAQLKNTNQKKELEVDCGL
  DKSNCGKQQNHTLDYNLAPGPLGRGTMPGKFPHSDKSLGEKAPLRLHSEKPECRISAICS
  PRDSMYQSVCLISEERNECVIATEV
• Function: Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types. During spinal cord neurogenesis, inhibits V2a interneuron fate. Involved in the Notch signaling pathway as Notch ligand.
• KEGG Pathway: Notch signaling pathway (hsa04330)
• Reactome Pathway:
  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)
  NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096)
  M1580_K2555) Translocation Mutant (9)(NOTCH1)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dilpacimab	DMCATH2	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
ABT-165	DMQ3O1U	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
Navicixizumab	DMZ2G69	Colorectal cancer	2B91.Z	Phase 1	[4]
NOV1501	DME2QUZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
OMP-21M18	DMX1D0S	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
REGN-421	DMWJ0IH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

References

• [1] J Clin Oncol 31, 2013 (suppl; abstr 2502).
• [2] Apoptogenic activity of 2alpha,3alpha-dihydroxyurs-12-ene-28-oic acid from Prunella vulgaris var. lilacina is mediated via mitochondria-dependent activation of caspase cascade regulated by Bcl-2 in human acute leukemia Jurkat T cells. J Ethnopharmacol. 2011 Jun 1;135(3):626-35.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer. BMB Rep. 2020 Nov;53(10):533-538.
• [6] National Cancer Institute Drug Dictionary (drug id 614677).