Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Neuropilin-1 (NRP1)
• Synonyms: Vascular endothelial cell growth factor 165 receptor; VEGF165R; Platelet-derived endothelial cell growth factor receptor; NRP; Membrane-bound; CD304
• Gene Name: NRP1
• DTT Type: Successful target; [1]
• BioChemical Class: Neuropilin and tolloid-like
• UniProt ID: NRP1_HUMAN
• TTD ID: T15023
• Sequence:
  MERGLPLLCAVLALVLAPAGAFRNDKCGDTIKIESPGYLTSPGYPHSYHPSEKCEWLIQA
  PDPYQRIMINFNPHFDLEDRDCKYDYVEVFDGENENGHFRGKFCGKIAPPPVVSSGPFLF
  IKFVSDYETHGAGFSIRYEIFKRGPECSQNYTTPSGVIKSPGFPEKYPNSLECTYIVFVP
  KMSEIILEFESFDLEPDSNPPGGMFCRYDRLEIWDGFPDVGPHIGRYCGQKTPGRIRSSS
  GILSMVFYTDSAIAKEGFSANYSVLQSSVSEDFKCMEALGMESGEIHSDQITASSQYSTN
  WSAERSRLNYPENGWTPGEDSYREWIQVDLGLLRFVTAVGTQGAISKETKKKYYVKTYKI
  DVSSNGEDWITIKEGNKPVLFQGNTNPTDVVVAVFPKPLITRFVRIKPATWETGISMRFE
  VYGCKITDYPCSGMLGMVSGLISDSQITSSNQGDRNWMPENIRLVTSRSGWALPPAPHSY
  INEWLQIDLGEEKIVRGIIIQGGKHRENKVFMRKFKIGYSNNGSDWKMIMDDSKRKAKSF
  EGNNNYDTPELRTFPALSTRFIRIYPERATHGGLGLRMELLGCEVEAPTAGPTTPNGNLV
  DECDDDQANCHSGTGDDFQLTGGTTVLATEKPTVIDSTIQSEFPTYGFNCEFGWGSHKTF
  CHWEHDNHVQLKWSVLTSKTGPIQDHTGDGNFIYSQADENQKGKVARLVSPVVYSQNSAH
  CMTFWYHMSGSHVGTLRVKLRYQKPEEYDQLVWMAIGHQGDHWKEGRVLLHKSLKLYQVI
  FEGEIGKGNLGGIAVDDISINNHISQEDCAKPADLDKKNPEIKIDETGSTPGYEGEGEGD
  KNISRKPGNVLKTLDPILITIIAMSALGVLLGAVCGVVLYCACWHNGMSERNLSALENYN
  FELVDGVKLKKDKLNTQSTYSEA
• Function: It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF165 isoform of VEGFA and VEGFB. Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulate VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development. The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system.
• KEGG Pathway:
  Axon guidance (hsa04360)
  HTLV-I infection (hsa05166)
• Reactome Pathway:
  CRMPs in Sema3A signaling (R-HSA-399956)
  CHL1 interactions (R-HSA-447041)
  Neurophilin interactions with VEGF and VEGFR (R-HSA-194306)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pegaptanib	DMOWEBU	Neovascular age-related macular degeneration	9B78.3Z	Approved	[2]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP1948	DMC80LV	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
RG7347	DMOE5NQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
H-KPPR-OH	DMDINX9	Discovery agent	N.A.	Investigative	[4]

References

• [1] Neuropilin-1 as Therapeutic Target for Malignant Melanoma. Front Oncol. 2015; 5: 125.
• [2] Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov. 2006 Feb;5(2):123-32.
• [3] National Cancer Institute Drug Dictionary (drug name ASP1948).
• [4] Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction. J Med Chem. 2010 Mar 11;53(5):2215-26.