Target Information
| Target General Information | Top | |||||
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| Target ID |
T15023
(Former ID: TTDC00183)
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| Target Name |
Neuropilin-1 (NRP1)
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| Synonyms |
Vascular endothelial cell growth factor 165 receptor; VEGF165R; Platelet-derived endothelial cell growth factor receptor; NRP; Membrane-bound; CD304
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| Gene Name |
NRP1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Retinopathy [ICD-11: 9B71] | |||||
| 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.
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| BioChemical Class |
Neuropilin and tolloid-like
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| UniProt ID | ||||||
| Sequence |
MERGLPLLCAVLALVLAPAGAFRNDKCGDTIKIESPGYLTSPGYPHSYHPSEKCEWLIQA
PDPYQRIMINFNPHFDLEDRDCKYDYVEVFDGENENGHFRGKFCGKIAPPPVVSSGPFLF IKFVSDYETHGAGFSIRYEIFKRGPECSQNYTTPSGVIKSPGFPEKYPNSLECTYIVFVP KMSEIILEFESFDLEPDSNPPGGMFCRYDRLEIWDGFPDVGPHIGRYCGQKTPGRIRSSS GILSMVFYTDSAIAKEGFSANYSVLQSSVSEDFKCMEALGMESGEIHSDQITASSQYSTN WSAERSRLNYPENGWTPGEDSYREWIQVDLGLLRFVTAVGTQGAISKETKKKYYVKTYKI DVSSNGEDWITIKEGNKPVLFQGNTNPTDVVVAVFPKPLITRFVRIKPATWETGISMRFE VYGCKITDYPCSGMLGMVSGLISDSQITSSNQGDRNWMPENIRLVTSRSGWALPPAPHSY INEWLQIDLGEEKIVRGIIIQGGKHRENKVFMRKFKIGYSNNGSDWKMIMDDSKRKAKSF EGNNNYDTPELRTFPALSTRFIRIYPERATHGGLGLRMELLGCEVEAPTAGPTTPNGNLV DECDDDQANCHSGTGDDFQLTGGTTVLATEKPTVIDSTIQSEFPTYGFNCEFGWGSHKTF CHWEHDNHVQLKWSVLTSKTGPIQDHTGDGNFIYSQADENQKGKVARLVSPVVYSQNSAH CMTFWYHMSGSHVGTLRVKLRYQKPEEYDQLVWMAIGHQGDHWKEGRVLLHKSLKLYQVI FEGEIGKGNLGGIAVDDISINNHISQEDCAKPADLDKKNPEIKIDETGSTPGYEGEGEGD KNISRKPGNVLKTLDPILITIIAMSALGVLLGAVCGVVLYCACWHNGMSERNLSALENYN FELVDGVKLKKDKLNTQSTYSEA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T36U0M | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Pegaptanib | Drug Info | Approved | Neovascular age-related macular degeneration | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | ASP1948 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 2 | RG7347 | Drug Info | Phase 1 | Solid tumour/cancer | [6] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | ASP1948 | Drug Info | [8] | |||
| 2 | H-KPPR-OH | Drug Info | [9] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | RG7347 | Drug Info | [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Axon guidance | |||||
| 2 | HTLV-I infection | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Axon guidance mediated by semaphorins | |||||
| PID Pathway | [+] 3 PID Pathways | + | ||||
| 1 | VEGF and VEGFR signaling network | |||||
| 2 | Plexin-D1 Signaling | |||||
| 3 | VEGFR1 specific signals | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Neurophilin interactions with VEGF and VEGFR | |||||
| 2 | CRMPs in Sema3A signaling | |||||
| 3 | CHL1 interactions | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | miR-targeted genes in squamous cell - TarBase | |||||
| 2 | miR-targeted genes in muscle cell - TarBase | |||||
| 3 | miR-targeted genes in lymphocytes - TarBase | |||||
| 4 | miR-targeted genes in epithelium - TarBase | |||||
| 5 | Signaling by VEGF | |||||
| 6 | Semaphorin interactions | |||||
| 7 | L1CAM interactions | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Neuropilin-1 as Therapeutic Target for Malignant Melanoma. Front Oncol. 2015; 5: 125. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6836). | |||||
| REF 3 | Future pharmacological treatment options for nonexudative and exudative age-related macular degeneration. Expert Opin Emerg Drugs. 2005 Feb;10(1):119-35. | |||||
| REF 4 | Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov. 2006 Feb;5(2):123-32. | |||||
| REF 5 | ClinicalTrials.gov (NCT04094506) Study of ASP1948, Targeting an Immune Modulatory Receptor, in Japanese Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027393) | |||||
| REF 7 | Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. | |||||
| REF 8 | National Cancer Institute Drug Dictionary (drug name ASP1948). | |||||
| REF 9 | 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. | |||||
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