IndraLab

Statements

VEGFA binds NRP1. 437 / 567
1 9 5 1 | 1 229 191
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"Compounds 16 and 17 displayed more than 60% inhibition and were more active than the EG00229 control (compound 21 ), a known antagonist that prevents VEGF-A binding to NRP1 and has also been shown to block spike protein binding to NRP1."
35215277
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"Nrp1 −/− hindbrains showed some defasciculation of these dorsolateral axons, but they were still clearly present in the mutant, suggesting that this are a suitable model to examine VEGFA isoform binding to NRP1."
25519242
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"To determine the effect of proteolytic activation of Sema3F on anti-angiogenic potency, we tested the ability of C-Sema to competitively block VEGF-A binding to neuropilin."
20387901
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"Nrp1 Associated With VEGFR2 in Response to Both sema3C and VEGF-A 165."
18723443
sparser
"While the b1 domain is essential to bind VEGF-A as deletion of this domain abrogates VEGF-A binding to NRP1, loss of the b2 domain only reduces NRP1 affinity to VEGF-A [ xref ]."
32911833
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"Binding of VEGF-A 165 to Nrp1 induces VEGF-A, VEGFR-2, and Nrp1 complex formation, receptor internalization, and recycling back to the membrane."
25018786
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"The ability of C-furSema and C-furSema Mon to competitively block VEGF-A binding to Nrp1 was compared (XREF_FIG)."
24079887
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"Disruption of VEGF-A binding to Nrp1 has previously been linked with reduced Nrp1 expression in various different mouse tissues 21."
28835631
sparser
"VEGF-A and NRP-1 interaction."
26804163
sparser
"However, neuropilin-1 binds VEGF121 in human endothelial cells in vitro (Pan et al., xref )."
33584205
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"(A) NRP1 protein in the NRP1–VEGF-A complex; (B) VEGF-A ligand in the NRP1–VEGF-A complex; (C) NRP1 protein in the NRP1–S1 complex; (D) NRP1 protein in the NRP1–R complex; (E) NRP1 protein in the NRP1–HRG complex; (F) NRP1 protein in the NRP1–RRRR complex; (G) NRP1 protein in the NRP1–RRAK complex; (H) NRP1 protein in the NRP1–RRAR complex; (I) NRP1 protein in the NRP1–RRAH complex; (J) NRP1 protein in the NRP1–TKPR complex; (K) NRP1 protein in the NRP1–TKPPR complex; (L) NRP1 protein in the NRP1–PPR complex; (M) NRP1 protein in the NRP1–PPRV complex; (N) NRP1 protein in the NRP1–PPR(V) complex; (O) NRP1 protein in the NRP1–EG0029 complex; (P) NRP1 protein in the NRP1– RRAA complex; (Q) NRP1 protein in the NRP1–RAAR complex; (R) NRP1 protein in the NRP1–ARAR complex.Figure 3: The percentage of simulation time during which intermolecular polar contacts were retained between NRP1 and the peptides in three independent 1 μs runs of: (A) NRP1–RRAK; (B) NRP1–RRAH; (C) NRP1–RRRR; (D) NRP1–RRAR; (E) NRP1–VEGF-A; (F) NRP1–S1; (G) NRP1–R; (H) NRP1–HRG."
34722943
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"17 VEGF-A binds VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), and co-receptors neuropilin 1 and 2 (NRP1 and NRP2)."
22958493
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"We reported that blocking the interaction between the membrane receptor Neuropilin 1 (NRP1) and VEGF-A blocked VEGF-A mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model."
36729125
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"This suggests that VEGFA helps to promote the activation of primordial follicles from the resting state but that this regulation does not appear to require NRP1 binding, although VEGFA binding to NRP1 might help stimulate the development of follicles to the primary state."
22322423
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"In comparison, EG00229 inhibited the NRP-1/VEGF-A interaction with an IC50value of 930 nM in our cell-free assay (Figure 6B)."
33787218
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"With no direct VEGFR2 and NRP1 binding interface identified, NRP1 is thought to modulate VEGFR2 through forming a multimeric complex bridged by NRP binding VEGF-A isoforms."
29690653
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"In addition, the binding of VEGF-A and NRP-1 increased after VEGF 165 recombinant protein was re-added to the CM ( xref , bottom )."
27364975
sparser
"sNRP-1 inhibition of VEGF-A-NRP1 interaction was found to result in tumor cell death xref ."
33815686
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"This allows the selective targeting of VEGF-A and NRP -1 interaction without affecting the binding of class 3 semaphorins."
26090340
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"However, this interaction alone is insufficient to explain the marked difference in potency of VEGF-A binding to Nrp1 and Nrp2, therefore other molecular determinants of this preferential binding must exist."
23145112
sparser
"Such mutant/WT heterodimers would have a reduced capacity to bind VEGF-A 165 , and this in turn would be predicted to impair biological functions and signaling dependent on VEGF-A 165 binding to NRP1 or on NRP2."
21653826
sparser
"VEGF-A binding to the dimeric complex of its receptor VEGFR2 and co-receptor NRP-1 triggers phosphorylation of the VEGFR2 cytoplasmic domain at Y1175 (Figure 7A)."
33787218
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"Mice lacking NRP1 or NRP1 binding VEGF-A isoforms have defective RGC axon organisation alongside brain vascular defects."
28676569
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"In addition, the natural product compound 17, an ester of 3,4-dihydroxycinnamic acid which docked in binding in mode II, was also more effective in disrupting the VEGF-A/NRP-1 interaction than EG00229."
33787218
sparser
"However, genetic ablation of Vegfa in the neuroepithelium does not phenocopy the vascular defects in Nrp1 mutant mice ( xref ), and antibody-mediated inhibition of Nrp1-Vegfa interactions does not block angiogenesis ( xref )."
26586223
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"We evaluated the ability of hit compounds to interfere with the NRP-1/VEGF-A interaction using an enzyme linked immunosorbent assay (ELISA)."
32995772
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"Multiple C-terminal arginine containing peptides and peptido-mimetics have been produced as competitive antagonists of VEGF-A and Nrp1 binding."
24079887
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"The transmembrane protein NRP1 (neuropilin 1) is present on both blood vessels and nerves and binds two structurally diverse ligands, the class 3 semaphorin SEMA3A and an isoform of the vascular endothelial growth factor VEGF-A termed VEGF (165) (VEGF (164) in mice)."
19909252
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"As expected, VEGF-A 109 did not bind to NRP-1, in contrast all Vammin proteins and VEGF-A 165 bound NRP-1."
28717175
sparser
"In Michigan Cancer Foundation-7 (MCF-7) breast cancer cells, Nrp1-VEGF-A signals through wingless/integrated protein (Wnt)/β-catenin pathways, to confer stemness and chemoresistance ( xref )."
36203599
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"Members of the VEGF family bind to the VEGFRs or co-receptors with different affinities : VEGF-A primarily binds to VEGFR-1, VEGFR-2, NRP-1 and NRP-2, while VEGF-B binds to VEGFR-1 and NRP-1."
29734653
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"This was evidenced by depleting the cell culture of exogenous VEGF-A(165), and using instead for routine culture VEGF-A(121), which does not interact with NRP-1, and by the inability of VEGF-A sequestering antibodies to inhibit the angiogenic activity of the NRP proteins."
20956519
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"[XREF_BIBR - XREF_BIBR] Binding of VEGFA to NRP1 promotes RhoA activation and then, activated RhoA contributes to the degradation of p27kip1, which in turn, promotes tumor cell proliferation."
33177389
sparser
"Figure 3: The percentage of simulation time during which intermolecular polar contacts were retained between NRP1 and the peptides in three independent 1 μs runs of: (A) NRP1–RRAK; (B) NRP1–RRAH; (C) NRP1–RRRR; (D) NRP1–RRAR; (E) NRP1–VEGF-A; (F) NRP1–S1; (G) NRP1–R; (H) NRP1–HRG."
34722943
sparser
"Blocking VEGFA 165 binding to NRP1 using a selective NRP1 inhibitor, ATWLPPR Peptide TFA (trifluoroacetic acid) (42), inhibited migration, although this effect did not reach statistical significance and NRP1 inhibition did not significantly affect VEGFA 165 -induced proliferation ( fig."
33239293
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"Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1, but not with an antibody that blocks VEGF-A binding to Nrp-1, resulted in a complex phenotype of impaired lymphatic vessel function, enhanced perivascular cell coverage and abnormal lymphatic vessel and valve morphology."
22723300
sparser
"It interacts with the extracellular b1b2 domain of NRP1 and has been identified as a specific inhibitor of NRP1 interaction with VEGFA."
33177389
biogrid
No evidence text available
20363638
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"Cells were stimulated with VEGF-A, which binds to Flt-1, KDR and NRP-1, and VEGF-C, which binds to KDR only."
11968003
sparser
"As we previously reported, a peptidic approach using amino-acid sequences derived from VEGF-A 165 (the end of exon-7 and exon-8) is crucial to define specific peptide sequences able to antagonize VEG[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26362351
sparser
"Figure 5: The percentage of simulation time during which intermolecular hydrophobic contacts were retained between NRP1 and the peptides in three independent 1 μs runs of: (A) NRP1–RRAR; (B) NRP1–RRAK; (C) NRP1–RRAH; (D) NRP1–VEGF-A; (E) NRP1–S1; (F) NRP1–PPR; (G) NRP1–PPRV; (H) NRP1– PPR(V); (I) NRP1–TKPPR; (J) NRP1–TKPR; (K) NRP1–RRAA; (L) NRP1–RAAR; (M) NRP1–ARAR."
34722943
sparser
"VEGF121 can also bind NRP1 in vitro, although with 50-fold lower affinity than VEGF165, because it lacks an exon 7-encoded domain that enhances NRP1 binding ( xref )."
26222953
sparser
"We found that 3 hit compounds blocked more than 50% of VEGF-A binding to NRP-1."
32995772
sparser
"VEGFA binds NRP1, which forms a complex with KDR on endothelial cells to initiate intracellular signaling associated with the proliferation, migration, and survival of endothelial cells ( xref ; xref ; xref )."
31791659
sparser
"The only significant hydrophobic contact exhibited by NRP1-VEGF-A is between Pro212 of VEGF-A and Tyr297 of NRP1 (Figure 5D), this interaction is observed across all three runs."
34722943
sparser
"Indeed, the results observed using therapies that prevent the binding of VEGF-A to NRP-1 can be likely attributed also to the blockade of the interaction of NRP-1 with ligands that share with VEGF-A the same NRP-1 binding site."
26090340
reach
"We used the anti-Nrp-1A antibody which specifically blocks the binding of Sema3A to Nrp-1, as well as the anti-Nrp-1B antibody which specifically blocks the binding of VEGF-A to Nrp-1 XREF_BIBR, XREF_BIBR."
22723300
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"36 This discovery is based on the grounds of the pain-relieving activity of SARS-CoV-2, which is suggested to mediate the interactions of NRP1 with S-protein by preventing the normal binding of a protein called VEGF-A to NRP1 and blocking pain signals to give pain relief."
33986591
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"NRP1 binds to VEGF-A and acts as a co-receptor of VEGFRs XREF_BIBR."
28216678
hprd
No evidence text available
9529250
hprd
No evidence text available
17222790
reach
"These data indicated that regorafenib and SC-78 reduced VEGF-A production and secretion, resulting in decreasing the binding of VEGF-A and NRP -1 and further affecting TNBC cell migration."
27364975
sparser
"However, an anti-NRP-1 humanized antibody that hampers VEGF-A binding to NRP-1, even though well-tolerated as single agent, showed modest clinical activity [ xref ]."
28977999
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"(A) NRP1 protein in the NRP1-VEGF-A complex; (B) VEGF-A ligand in the NRP1-VEGF-A complex; (C) NRP1 protein in the NRP1-S1 complex; (D) NRP1 protein in the NRP1-R complex; (E) NRP1 protein in the NRP1-HRG complex; (F) NRP1 protein in the NRP1-RRRR complex; (G) NRP1 protein in the NRP1-RRAK complex; (H) NRP1 protein in the NRP1-RRAR complex; (I) NRP1 protein in the NRP1-RRAH complex; (J) NRP1 protein in the NRP1-TKPR complex; (K) NRP1 protein in the NRP1-TKPPR complex; (L) NRP1 protein in the NRP1-PPR complex; (M) NRP1 protein in the NRP1-PPRV complex; (N) NRP1 protein in the NRP1-PPR(V) complex; (O) NRP1 protein in the NRP1-EG0029 complex; (P) NRP1 protein in the NRP1-RRAA complex; (Q) NRP1 protein in the NRP1-RAAR complex; (R) NRP1 protein in the NRP1-ARAR complex."
34722943
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"[XREF_BIBR] Pan et al [XREF_BIBR] using a mouse xenograft tumor model, determined that antibodies that blocked VEGFA binding to NRP1 enhanced the anti-tumor effect of anti-VEGFA antibodies."
33177389
sparser
"Blocking VEGFA 165 binding to NRP1 using a selective NRP1 inhibitor, ATWLPPR Peptide TFA (trifluoroacetic acid) ( xref ), inhibited migration, although this effect did not reach statistical significance and NRP1 inhibition did not significantly affect VEGFA 165 -induced proliferation (fig."
33239293
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"Importantly, although inhibition of the VEGF-A binding to Nrp-1 did not influence lymphatic vessel development, the formation of small blood vessels was impaired, in agreement with the previously reported effects of this antibody 24 - therefore confirming the activity of the antibody."
22723300
reach
"It is notable that VEGF-A binds to both NRP-1 and NRP-2, but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 (Figure 1B, C) ."
32995772
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"Nrp-1 also binds the VEGF-A splice isoform VEGF165, stimulates angiogenesis, and is necessary for vascular development in the mouse."
15376331
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"Selective ablation of Nrp1 in endothelial cells leads to angiogenic sprouting defects that occur independently of semaphorins, suggesting that impaired Nrp1 binding to Vegfa is the primary defect."
26586223
sparser
"In contrast, VEGF121, which does not bind to NRP1, did not support complex formation."
11948691
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"VEGF-A signals through its main receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1 or Kdr), and also interacts with the co-receptors Neuropilin 1 and 2 (Nrp-1/2)."
23620236
sparser
"We show that charge reversal produces a decrease in Nrp1 binding to VEGF-A indicating a direct contribution to ligand binding selectivity."
23145112
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"In vascular development, VEGF-A binds to VEGFR1 and VEGFR2, and NRP1 and NRP 2; VEGF-B binds to VEGFR1 and NRP1; and VEGF-C and VEGF-D bind to VEGFR2, VEGFRR3, and NRP2."
23445813
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"Binding of VEGF-A to NRP-1 plays a critical role in pathological angiogenesis and tumor progression."
24961874
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"Interestingly, C-end rule peptides with a C-terminal arginine residue in a configuration similar to that of VEGF-A bind NRP1 to induce vascular permeability [XREF_BIBR], and this property may be exploited to enhance tumor penetration of chemotherapeutic drugs [XREF_BIBR]."
24521511
biogrid
No evidence text available
22318724
reach
"Such normal vessel morphology was observed in mice that were treated in utero with control IgG and in mice treated in utero with anti-Nrp-1B (which blocks VEGF-A binding to Nrp-1)."
22723300
sparser
"In the NRP1-VEGF-A complex, NRP1 residues exhibit limited fluctuation, with overall RMSF below 3 Å; with regions spanning residues 280–285, 310–312, 375–380 and the loop III region (345–354) showing slightly higher RMSF relative to other regions of the protein (Figure 2A)."
34722943
sparser
"In the NRP1-VEGF-A complex, NRP1 residues exhibit limited fluctuation, with overall RMSF below 3 Å; with regions spanning residues 280–285, 310–312, 375–380 and the loop III region (345–354) showing slightly higher RMSF relative to other regions of the protein ( xref A)."
34722943
sparser
"At a minimum, the identified compounds share a 2(1H)-pyridone core, and those with 'pyridone and pyrimidone cores' inhibited VEGF-A-NRP-1 binding with higher efficiency than EG00229; and as efficient as the SARS-CoV-2 S glycoprotein association with NRP-1."
| DOI
trips
"It was concluded that an intact b1b2 domain serves as the VEGF165-, PlGF-2-, and heparin-binding sites in NRP1, and that heparin is a critical component for regulating VEGF165 and PlGF-2 interactions with NRP1 by physically interacting with both receptor and ligands."
11986311
reach
"Blocking of Vegf binding to Nrp1 using a specific antibody that leaves Vegf binding to Vegfr2 intact XREF_BIBR does not phenocopy the retinal angiogenesis defects in Nrp1 mutants described here, and Nrp1 promotes activation of intracellular c-abl activation in a VEGF independent manner XREF_BIBR, further supporting the idea that Nrp1 may affect other pathways that trigger tip cell formation."
26081042
reach
"The expected results were the identification of full-antagonist peptides able to switch-off phactr-1 mRNA in HUVEC through the total or partial VEGF-A 165 / VEGF-R1 and NRP-1 binding inhibition since [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26362351
reach
"Alternatively, the interaction of NRP-1, VEGF-A, and SARS-CoV2 may be responsible for part of the presented symptoms 11 : blocking the binding site of VEGF-A to NRP-1, as described for SARS-CoV2 spike protein, could ameliorate or prevent proper pain sensation in affected patients."
35295965
reach
"In addition to the tyrosine kinase receptors, VEGF-A binds to co-receptor neuropilin-1 (NRP-1)."
22087332
reach
"These data are consistent with a recent study reporting a dissociation constant (K d) of 5.2 nM for NRP2, compared with the K d for VEGF-A 165 binding to NRP1 of 0.2-0.3 nM."
21653826
sparser
"After docking and two rounds of similarity search computations, we identified 4 compounds that inhibit the biotinylated VEGF-A₁₆₅ binding to recombinant NRP-1 with Ki of about 10 μM. These compounds contain a common chlorobenzyloxy alkyloxy halogenobenzyl amine scaffold that can serve as a base for further development of new NRP-1 inhibitors."
24961874
sparser
"VEGF-A interacts with NRP-1 and this leads to enhanced VEGF-A interaction with VEGFR, leading to enhanced angiogenesis. xref – xref Consistent with this role, NRP-1 overexpression increases blood vessel formation, xref and inactivation causes abnormal vasculature formation leading to embryonic lethality. xref NRP-1 is expressed in various human tumors, including prostate cancer, breast cancer, melanoma and pancreatic adenocarcinoma. xref – xref In some model systems, NRP-1 expression increases angiogenesis and tumor formation; xref , xref however, how NRP-1 regulates tumor formation is not well understood."
26804163
sparser
"VEGF-A binding to the dimeric complex of its receptor VEGFR2 and co-receptor NRP-1 triggers phosphorylation of the VEGFR2 cytoplasmic domain at Y1175 ( xref A)."
33787218
reach
"In this context, a human mAb (i.e., MNRP1685A) that blocks the binding of VEGF-A, VEGF-B, and PlGF to NRP-1 is currently under evaluation in clinical trials."
26090340
sparser
"NRP1 bound VEGF-A 165 , but not VEGF 121 because VEGF-A 121 lacked the exon 7-encoded region."
26209534
sparser
"These data are consistent with a recent study reporting a dissociation constant ( K d ) of 5.2 nM for NRP2, compared with the K d for VEGF-A 165 binding to NRP1 of 0.2–0.3 nM ( xref ; xref )."
21653826
reach
"NRP-1 binding to several VEGF-A isoforms promotes growth factor interaction with VEGF receptor (VEGFR)-2, increasing receptor phosphorylation."
34252269
reach
"The overexpression of NRP1 in olfactory cells also makes it Disrupting the key protein-protein interactions between NRP1 and VEGF-A at the b1 CendR binding site has long been the focus of drug discovery efforts, particularly for cancer therapy."
35215277
reach
"Alternatively, NRP and VEGFA complexes binding to FLT1 can also prevent endothelial cell migration and vascular development so there are potentially many check points that are present within the testis to prevent over-vascularization to ensure development of the seminiferous cords."
26562337
sparser
"Here, we demonstrated that both regorafenib and SC-78 could decrease the endogenous level of VEGF-A and the inhibition of secreted VEGF-A would further reduce the binding of VEGF-A to receptor NRP-1, which might lead to increased binding of SEMA3A and NRP-1 and reduce the migration of breast cancer cells."
27364975
sparser
"The only significant hydrophobic contact exhibited by NRP1-VEGF-A is between Pro212 of VEGF-A and Tyr297 of NRP1 ( xref D), this interaction is observed across all three runs."
34722943
sparser
"Solid tumor development is aided when NRP-1 binds VEGF-A, while SEMA3A binding often improves prognosis by limiting tumor cell motility and invasion."
35052853
sparser
"Our present studies suggest that VEGF-A interacts with NRP-1, via a novel signaling pathway that does not require VEGF receptors, to activate cellular processes in ECS cells that enhance ECS cell survival and tumor formation."
26804163
reach
"In addition to VEGFR2, VEGF-A also binds to VEGFR1 (or FLT1) and NRP1."
32547411
sparser
"Researchers have also elucidated that binding of VEGFA to NRP1 leads to the receptor interaction with GIPC1, a scaffold protein and subsequent formation of a complex with the RhoA GEF Syx ( xref )."
32377503
sparser
"C-furSema, representing the processed form of Sema3F, was able to fully inhibit the binding of AP-VEGF-A to neuropilin."
20387901
reach
"XREF_BIBR, XREF_BIBR VEGF-A can bind to VEGFR-1, VEGFR-2, and NRP-1."
25767397
sparser
"Vegfa binding to Nrp1 is a trigger for several of the biological functions of Vegfa xref ; therefore, the inverse co-relation in Vegfa - Nrp1 expression in Vgat ECKO endothelial cells is particularly interesting."
31700116
reach
"NRP1 bound VEGF-A 165, but not VEGF 121 because VEGF-A 121 lacked the exon 7 encoded region."
26209534
reach
"KDR can utilize NRP1 bound to VEGFA angiogenic isoforms as a bridge to enhance signal transduction and also allow for appropriate trafficking of NRP1 within the cell to allow for receptor recycling."
26562337
sparser
"Nrp-1 also binds with high affinity to VEGFR-1, which counteracts an interaction of VEGF-A and Nrp-1 and finally results in reduced VEGF-A effectiveness [ xref ]."
23475067
reach
"Using a novel chimeric C-furSema, we demonstrate that combining a single C-terminal arginine with the helical motif is necessary and sufficient for potent inhibition of VEGF-A binding to Nrp1."
24079887
reach
"Examples of concentration–response curves of inhibition of the NRP-1/VEGF-A interaction for two compounds (4, 5) are shown in Figure 6A."
33787218
sparser
"Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells."
20151671
sparser
"VEGF-A interacting with NRP1 could regulate Hippo signaling to drive tumor cell survival, angiogenesis, and tumor formation through facilitating the stabilization of YAP1 [ xref ]."
32046779
reach
"Surprisingly, blockade of Sema3A, but not of VEGF-A binding to Nrp-1 had a profound effect on the development of lymphatic vessels, leading to their impaired maturation and function."
22723300
sparser
"Though TKPR has been reported to disrupt the NRP1-VEGF interface (von Wronski, 2006), the results of the present study cannot conclusively support that finding given the inconsistency of binding affinity scores across the three simulations of NRP1-TKPR (-23.67 ± 11.80 kcal/mol, -67.33 ± 5.31 kcal/mol, -51.48 ± 19.13 kcal/mol) and NRP1-VEGF-A (-85.81 ± 18.66 kcal/mol, -67.34 ± 11.27 kcal/mol, -82.07 ± 18.59 kcal/mol)."
34722943
sparser
"To exclude that impaired VEGFR2 phosphorylation simply reflects a reduced affinity of NRP1 cyto for VEGF-A 165 , we used an established method that tests binding of NRP1 ligands such as alkaline phosphatase-conjugated VEGF-A 165 to NRP1-expressing axons and vessels in vivo ( xref )."
23639442
reach
"Additionally, a VEGF-A splice variant; VEGF-A 165 uniquely binds to co-receptor neuropilin-1 (NRP-1) and significantly enhances its availability and binding to VEGFR-2 [XREF_BIBR]."
28974056
sparser
"Thus, five of the synthetic and one of the natural compounds significantly inhibited the interaction between VEGF-A and NRP-1, confirming that they compete for binding to the CendR site ( xref )."
33787218
reach
"Most importantly, when appropriately decorated, compounds 4, 5, 8, 2, and 9 were found to disrupt the VEGF-A/NRP-1 interaction more effectively than EG00229."
33787218
sparser
"However a thiophene-based scaffold 30 had an IC 50 of 13 μM for inhibition of VEGF-A 165 binding to NRP1."
20151671
sparser
"We demonstrated that IDB0076 simultaneously binds to human VEGFA and human NRP1 in vitro and inhibits the effects of both VEGFA and other angiogenesis growth factors in cell-based assays."
32560565
sparser
"These findings provide strong evidence for the importance of VEGF-A 165 binding to NRP1 in endothelial cell migration, and also highlight the role of NRP1 in linking the VEGF-A 165 /KDR axis to specific chemotactic signaling pathways."
21653826
sparser
"In addition, NRP1 binds to vascular endothelial growth factor-A (VEGF-A), whereas NRP2 binds to VEGF-C and –D [ xref – xref ]."
35776228
reach
"Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition."
23145112
reach
"Strikingly, C-furSema Het was as potent as C-furSema at inhibiting VEGF-A-dependent activation of endothelial cells (XREF_FIG) and VEGF-A binding to Nrp1 (XREF_FIG, IC 50 = 35 +/- 3 nM and 24 +/- 1 nM, respectively)."
24079887
reach
"Indeed, the results observed using therapies that prevent the binding of VEGF-A to NRP-1 can be likely attributed also to the blockade of the interaction of NRP-1 with ligands that share with VEGF-A the same NRP-1 binding site."
26090340
sparser
"NRPa-308, discovered by its ability to inhibit VEGFA binding to NRP1 [ xref ], is a better NRP2 inhibitor."
33461580
sparser
"Reduced binding of VEGF-A to Nrp1 has previously been shown to impair post-natal angiogenesis and arteriogenesis xref , xref ."
28835631
reach
"The ability of VEGFA to bind and activate these receptors is regulated by the co-receptor neuropilin-1 (NRP-1) which can directly bind VEGFA and function as a bridging molecule between ligand and receptor [XREF_BIBR, XREF_BIBR]."
22382924
reach
"Binding of VEGF-A to neuropilin 1 is essential for proangiogenic activity."
26122849
sparser
"Here we report, novel promising small drug-like molecules disrupting the binding of VEGF-A₁₆₅ to NRP-1."
24961874
reach
"It is of interest that we found fewer blood vessel capillaries in anti-Nrp-1B treated pups at day P5.5 (XREF_SUPPLEMENTARY), indicating that the formation of smaller blood vessels is impaired when VEGF-A binding to Nrp-1 is blocked, in line with previously reported effects of this antibody 24."
22723300
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"For example, during arterial-venous specification, VEGF-A binds to VEGFR2 and co-receptor neuropilin-1 (Nrp1), leading to activation of Notch signalling."
28181491
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"The best characterized of these is (S)-2-(3-(benzo [c] [1,2,5] thiadiazole-4-sulfonamido) thiophene-2-carboxamido)-5-((diaminomethylene) amino) pentanoic acid (EG00229), which has been previously identified as a specific inhibitor of the NRP1 and VEGF-A interaction."
29648813
reach
"Experiments are performed both in the absence and presence of the soluble ligand vascular endothelial growth factor A (VEGFA), which binds to both VEGFR2 and NRP1."
29630862
sparser
"This is in agreement with the proposal that a small molecule ligand that inhibits VEGF-A binding to NRP1 reduces the viability of A549 lung carcinoma cells in vitro xref ."
26147006
reach
"This NRP-1, due to its important role in tumour progression, triggered interest in the design of new molecules able to significantly inhibit NRP-1 and VEGF-A 165 interaction to suppress pathological angiogenesis."
30881620
sparser
"Thus, all the isoforms can bind the two main VEGFA tyrosine kinase receptors, VEGFR1 (FLT1) and VEGFR2 (KDR, previously also known as FLK1), while NRP1 binds with higher affinity the larger VEGFA isoforms, such as VEGFA165 and VEGFA189, compared to VEGFA121 by interacting with the heparin binding domain encoded by exon 7, even though the interaction between VEGFA and NRP1 also involves the exon 8 encoded epitope, which is common to all the isoforms [ xref , xref , xref , xref ]."
33947161
sparser
"This suggests that VEGFA helps to promote the activation of primordial follicles from the resting state but that this regulation does not appear to require NRP1 binding, although VEGFA binding to NRP1 might help stimulate the development of follicles to the primary state."
22322423
sparser
"VEGF-A 165 binding to NRP1 is required for FAK signaling."
21653826
sparser
"We hypothesize that the interactions of VEGF-A and NRP-1 directly affect cell growth, because the arrest of cell growth by TZDs has been widely reported."
20214829
sparser
"A high-affinity mAb targeting the coagulation factors domain of NRP-1 (anti-NRP-1B) has been shown to inhibit VEGF-A-induced migration of human endothelial cells and tumor formation in animal models avoiding VEGF-A-binding to NRP-1 ( xref – xref )."
26090340
reach
"Nrp1 was able to potently inhibit the binding of VEGF-A to Nrp1 affinity plates with an IC 50 = 1.8 microM (log IC 50 = -5.7 +/-0.2) (black line, XREF_FIG)."
23145112
reach
"Figure 6: Identification of nanomolar inhibitors of the NRP-1/VEGF-A interaction."
33787218
sparser
"It has been proposed that both VEGF-A 165 and VEGF-A 121 can bind NRP1; however, only VEGF-A 165 is believed to form a heteromeric complex with VEGFR2 and NRP1 ( xref )."
27044325
reach
"In the present study we determined the basis for preferential Nrp1 binding to VEGF-A."
23145112
reach
"Alternatively, the interaction of NRP-1, VEGF-A, and SARS-CoV2 may be responsible for part of the presented symptoms11: blocking the binding site of VEGF-A to NRP-1, as described for SARS-CoV2 spike protein, could ameliorate or prevent proper pain sensation in affected patients.11Obviously, we cannot completely rule out other reasons for the observed hypoalgesia, abnormal QST, and reduced intraepidermal fiber density."
35295965
reach
"VEGF-A binds to two tyrosine quinase receptors, named VEGFR-1 and VEGFR-2, and also to the coreceptor neuropilin-1."
30028320
sparser
"We next investigated the role of VEGF-A 165 binding to NRP1 in the migration of HUVECs."
21653826
reach
"Moreover, VEGF-A and PlGF binds to NRP-1 and enhances its affinity for VEGFR-2 [113]."
34502066
biogrid
No evidence text available
16423422
sparser
"As it was mentioned already, the amino acid Asp320 is very important for NRP1 to interact with different ligands and VEGF-A xref , xref , as well as for the CendR region in the SARS-CoV-2 xref , xref , therefore, the region between the amino acids Thr316, Asp320, Ser346, Thr349 and Tyr353 has a very important role for the S1 region of SARS-CoV-2 to interact with NRP1; in this study was carried out a docking directed to amino acids in the b1 region reported in the NRP1 (Thr316, Asp320, Ser346, Thr349 and Tyr353) xref , that is important to interact with the S-Protein (S1 region) of SARS-CoV-2 xref , since it has been shown that by preventing this interaction, the infectious process caused by this virus could be reduced xref , xref , xref ."
| PMC
sparser
"It exhibits submicromolar potency in inhibition of VEGF-A binding to NRP1 and good functional inhibition of VEGF driven angiogenesis, cell migration, tumor invasiveness, and notably Treg cell activation."
29648813
sparser
"These networks were enriched for genes in the signaling pathways of Rho GTPase small molecules, axon guidance, actin skeleton, VEGFA-NRP1 induced angiogenesis and the endothelin-1 pathway."
36055599
reach
"VEGFA binds the receptors VEGFR1 (Flt1), VEGFR2 (Flk1 and Kdr), and neuropilin-1, which are expressed by these angioblasts."
25918223
sparser
"Interaction between Nrp1 and VEGF-A also mediated promotion of cancer cell stemness."
36203599
reach
"In an in-silico screening of ∼480K small molecules binding to the extracellular b1b2 pocket of NRP1, we identified nine chemical series, with six compounds disrupting VEGF-A binding to NRP1."
36729125
sparser
"In addition, the binding of VEGF-A(165) to NRP-1 potentiates its capacity to promote PGI(2) synthesis."
15637071
sparser
"While all members of the family function in vascular development, only the interaction of VEGF-A with Nrp1 has been implicated in NCC biology."
25662260
sparser
"When VEGF-A binds to NRP1, it facilitates the interaction of NRP1 with GIPC1, a scaffold protein."
29659486
sparser
"Dysregulated CCEs which function as pivotal roles in tumorigenesis and development of HCC included SPP1-CD44, MIF-TNFRSF14, and VEGFA-NRP1."
35634447
reach
"Our finding that blocking NRP1 function with peptide N results in decrease in microvessel density and reduction of hepatic artery BFV indicates that liver expressed NRP1 is functional and may control [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21338642
reach
"Removal of a salt bridge between D142 and R164 implicated in VEGF-A binding to neuropilin-1 had a minor effect on potency."
24771685
reach
"VEGF-A binds to VEGFR2, and the co-receptors neuropilin 1 and 2 (NRP1 and NRP2), while VEGFR1 functions mostly as a decoy [10]."
31973092
sparser
"Blocking of Vegf binding to Nrp1 using a specific antibody that leaves Vegf binding to Vegfr2 intact xref does not phenocopy the retinal angiogenesis defects in Nrp1 mutants described here, and Nrp1 promotes activation of intracellular c-abl activation in a VEGF-independent manner xref , further supporting the idea that Nrp1 may affect other pathways that trigger tip cell formation."
26081042
reach
"These data suggest that the N-terminal region of C-furSema, centered around the conserved cysteine, contributes to potent competitive inhibition of VEGF-A binding to Nrp1."
24079887
sparser
"The well-documented NRP1/VEGF-A blocker EG00229 (Jarvis et al., 2010) was also studied to compare its NRP1 interaction with that of VEGF-A. Thus, in this study, to explore the stability and binding interactions of CendR peptides, seventeen systems were studied – VEGF-A, 13 peptides, a lone arginine, an arginine analogue and an NRP1 inhibitor (Table 1 and Figure 1C)."
34722943
sparser
"EG00229 inhibited VEGF-A binding to NRP-1, decreased VEGFR-2 phosphorylation and the migration of lung carcinoma cells in vitro ."
26090340
reach
"We coated plates with the extracellular domain of human NRP-1 (containing the a1a2 and the b1b2 regions) and added a selection of our compounds (based on SAR and commercial availability) to disrupt the NRP-1/VEGF-A interaction."
32995772
sparser
"Generation ofNrp1 Y297A mouse mutants revealed that VEGF-A binding to NRP1 is not essential for embryonic angiogenesis [ xref ] and mutants were born at normal Mendelian ratios."
32911833
reach
"Although NRP1 can bind all three major VEGF-A isoforms, VEGF 120 is too small to bridge the gap between Flk1 and NRP1 [XREF_BIBR], thus precluding complex formation."
21978864
sparser
"This drug inhibited VEGF-A binding to NRP1, and reduced the viability of A549 lung carcinoma cells."
22948112
sparser
"VEGF-A 165 binding to NRP1 is required for complex formation between NRP1 and KDR."
21653826
reach
"15 It is notable that VEGF-A binds to both NRP-1 and NRP-2 but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 ( Figure 1B ,C)."
33787218
reach
"VEGF-A also interacts with coreceptors heparin sulfate proteoglycans, neuropilin-1, and neuropilin-2, which are also located on the surface of endothelial cells."
26719668
reach
"Upon binding to VEGFR2, VEGF-A can interact with neuropilin-1, which induces the migration of HUVECs towards a VEGF-A gradient in a FAK dependent manner."
25173872
sparser
"Heparin increases VEGF-A 165 binding to NRP1 and promotes receptor dimerization of isolated proteins ( xref )."
21653826
sparser
"The well-documented NRP1/VEGF-A blocker EG00229 ( xref ) was also studied to compare its NRP1 interaction with that of VEGF-A. Thus, in this study, to explore the stability and binding interactions of CendR peptides, seventeen systems were studied – VEGF-A, 13 peptides, a lone arginine, an arginine analogue and an NRP1 inhibitor ( xref and xref C)."
34722943
reach
"XREF_BIBR, XREF_BIBR Our present studies suggest that VEGF-A interacts with NRP-1, via a novel signaling pathway that does not require VEGF receptors, to activate cellular processes in ECS cells that enhance ECS cell survival and tumor formation."
26804163
reach
"Indeed, the L1 loop of the Nrp b1 domain has been shown to contribute to the observed preferential binding of VEGF-A to Nrp1 XREF_BIBR."
23145112
sparser
"Amino acid residues Tyr297, Trp301, Thr316, Asp320, Ser346, Thr349, and Tyr353 were identified as critical for the SARS-CoV-2 binding and are virtually identical to the key interactions of VEGF-A 164 with NRP1 [ xref ]."
35215277
sparser
"We also identified predicted semaphorin-neuropilin 1 (Nrp1) interactions, Bmp4-Bmpr2 interactions, and Fgf1-Fgfr3 interactions in addition to Vegfa-Vegfr1 (Flt1), Vegfa-Vegfr2 (Kdr), and Vegfa-neuropilin 1 (Nrp1) interactions ( xref )."
32091393
reach
"NRP-1 is usually bound by vascular endothelial growth factor-A (VEGF-A), a - amongst other- pro-nociceptive factor."
| DOI
sparser
"Mutations in NRP1 b1 domain of tyrosine in position 297 into alanine (Y297A) or aspartic acid in position 320 into alanine (D320A) abrogate NRP1 binding to VEGF-A and reduces endothelial migration in vitro [ xref ]."
32911833
sparser
"A recent study suggests that VEGF121 also binds NRP1 in human endothelial cells that express KDR ( xref )."
21852397
reach
"XREF_BIBR, XREF_BIBR VEGF-A also binds to semaphorin receptor NRP1, XREF_BIBR a single spanning non tyrosine kinase transmembrane protein that functions as a VEGFR-2 co-receptor."
30557701
sparser
"To further analyse its role in arthritis-induced angiogenesis, we investigated whether NRP-1 function is required for the induction of endothelial cell migration by arthritic paw homogenates applying a neutralising antibody that specifically blocks the binding of VEGF121 and VEGF164 to NRP-1 [ xref , xref ]."
22817681
sparser
"Functional analysis of two binding deficient NRP1 mutants revealed an unexpected dominant negative effect of these mutants on VEGF-A 165 binding to WT NRP1 and on VEGF-A 165 stimulation of migration and signaling mediating cell migration."
21653826
sparser
"VEGF-A binding to NRP might be due to the exon 8 C-terminus KPR motif, which inserts into a negative cleft in the NRP b1 domain ( xref ) [ xref , xref ]."
18625544
reach
"Moreover, while both a Nrp1-binding VEGF-A isoform and Sema3A are expressed at the optic chiasm during RGC midline crossing, loss of VEGF164 expression significantly impaired RGC axon crossing at the optic chiasm in rodents [20]."
33477094
sparser
"Nrp-1 can bind VEGF-A 165 , VEGF-B, VEGF-E, and placental growth factor (PIGF)."
30197476
sparser
"Several groups have shown that binding of VEGF-A to NRP1 potentiates VEGF-A-mediated signalling in ECs."
32911833
reach
"Mutation of this region results in the largest net loss of VEGF-A binding to Nrp1, consistent with a direct interaction involving a hydrogen bond between Nrp1-T299 and VEGF-A-E154 XREF_BIBR."
23145112
hprd
No evidence text available
10409677
reach
"Most importantly, the binding hypotheses were confirmed as compounds with pyridone and pyrimidone cores, when appropriately decorated, were found to disrupt the VEGF-A/NRP-1 interaction more effectively than EG00229 and to a similar extent as SARS-CoV-2 Spike protein."
32995772
reach
"Thus, three of the synthetic compounds significantly inhibited the interaction between VEGF-A and NRP-1, confirming that they compete for binding to the CendR site (Table 1)."
32995772
sparser
"Figure 1: (A) Comparison of the binding modes of VEGF-A164 (in orange stick representation) and SARS-CoV-2 (in green stick representation) CendR motifs by superimposing VEGF-A-NRP1 (PDB ID: 4DEQ; [17] NRP1 in orange cartoon representation) and SARS-CoV-2-NRP1 (PDB ID: 7JJC; [6] NRP1 in green cartoon representation) complexes. (B) Zoomed view representing SARS-CoV-2 CendR binding mode into the b1 domain of NRP1, highlighting interactions with the key amino-acid residues (in green stick representation)."
35215277
reach
"Nrp1 was found to interact with VEGF-A 165 (and other VEGFs) and the receptor tyrosine kinase (RTK) VEGFR2, and to enhance signaling through this pathway and promote angiogenesis."
22948112
reach
"EG00229 is an inhibitor of VEGF-A and NRP -1 interaction."
30456845
sparser
"One of these compounds (56) demonstrated inhibition of VEGF-A 165 binding to NRP-1 (IC 50 =39μM) and specificity for NRP-1 over VEGF-R2."
27622745
reach
"These key binding residues are strongly supported by the alanine mutagenesis showing that Y297A, W301A, D320A, S346A, T349A, K351A, and Y353A result in a complete loss of biotinylated VEGF-A binding to NRP1 [19]."
34031621
reach
"In agreement, abolishing VEGF-A binding to NRP1 in Nrp1 Y297A and Y297A mice recapitulated the vascular extension defect caused by endothelial NRP1 loss in the P6 retina (XREF_FIG E, red arrow)."
26051942
reach
"Likewise, if NRP1 and VEGFA complexes bind to FLT1 this also may inhibit endothelial cell migration and the development of vasculature."
18638140
reach
"Moreover, treatment with EG00229, an inhibitor of VEGF-A and NRP -1 interaction, also reduces p38-P (XREF_FIG)."
30456845
reach
"Loss of NRP1 or NRP1 binding VEGF-A isoforms increases the proportion of RGC axons projecting ipsilaterally at the expense of contralateral projections, and axon organisation in the optic tracts is perturbed."
28676569
reach
"This drug inhibited VEGF-A binding to NRP1, and reduced the viability of A549 lung carcinoma cells."
22948112
sparser
"We reported that blocking the interaction between the membrane receptor Neuropilin 1 (NRP1) and VEGF-A blocked VEGF-A mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model."
36729125
reach
"The binding of VEGF-A to NRP1 enhances its affinity for VEGFR2."
25087623
reach
"VEGF-A binding to NRP1 induced the interaction between GIPC1 and Syx, thereby promoting DJM-1 proliferation."
26209534
reach
"This observation has been proposed to be due to defective VEGF-A binding to NRP1 on outflow tract endothelium [XREF_BIBR], agreeing with the observation that Vegfa 120/120 mice lacking NRP1 binding VEGF165 have similar defects [XREF_BIBR]."
24521511
sparser
"While heparin binding domain does not appear to bind to the soluble VEGF receptors xref , HBD binds to NRP and is required for VEGF-A 165 interaction with NRP, either independently or when in a complex with NRP and VEGF receptors where VEGF-A 165 bridges between VEGFR2 and NRP."
23409021
sparser
"We have shown that VEGF-A and NRP-1 are highly expressed in ECS cell tumors and that VEGF-A interacts with NRP-1 to stimulate ECS cell-associated tumor vascularization and growth [ xref ]."
29755126
sparser
"As expected, p13 inhibited the VEGF-A 165 binding to NRP-1 with the same p1 monomeric peptide efficiency (98 ± 2% vs 97 ± 2%) ( Fig. 2 B)."
26362351
reach
"VEGF-A 165 but not VEGF-A 121 interacts with neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2), which are cell surface transmembrane glycoprotein receptors [XREF_BIBR]."
17979880
sparser
"Following the same idea, a small-molecule inhibitor, EG00229, designed to target the ‘b1’ domain appeared to affect VEGF-A binding to NRP1 and the viability of A549 lung carcinoma cells. xref Interestingly, it also increased the potency of paclitaxel and 5-fluorouracil (5-FU)."
25285016
reach
"In addition, NRP1 binds to vascular endothelial growth factor-A (VEGF-A), whereas NRP2 binds to VEGF-C and –D [13–16]."
35776228
sparser
"Binding of VEGF-A to neuropilin 1 is essential for proangiogenic activity ( xref )."
26122849
sparser
"The potency of compound 2 in inhibiting VEGF-A binding to NRP1 was thus very similar to that of the bicyclic peptide compound 1 , which inhibits 125 I-VEGF-A binding to PAE/NRP1 and tumor cells with IC 50 values of 2−3 μM and inhibits 125 I-VEGF-A binding to HUVECs with an IC 50 of 20 μM.( xref )"
20151671
reach
"Thus, 2 was identified as a non peptide antagonist of VEGF-A binding to NRP1."
20151671
reach
"Tumor cell proliferation is induced by VEGF-A binding to NRP1 through a Ras dependent mechanism."
25285016
reach
"These studies suggest that VEGF-A interacts with NRP-1 and GIPC1 to regulate alpha6 and beta4-integrin, FAK, Src, PI3K and PDK1, LATS1 signaling to increase YAP1 and incrementNp63alpha accumulation to drive ECS cell survival, angiogenesis, and tumor formation."
29755126
sparser
"Further studies of the shortest active fragment of A7R led to a more elaborate branched peptidomimetic, Lys(hArg)-Dab-Pro-Arg, which was a stronger inhibitor of VEGF-A 165 binding with NRP-1, as determined by an in vitro ELISA assay, and was more stable in human serum compared to A7R [ xref ]."
35056995
sparser
"Binding of VEGF-A to NRP-1 plays a critical role in pathological angiogenesis and tumor progression."
24961874
sparser
"VEGF-A also binds to neuropilin 1 (NRP1), which presents VEGF-A to VEGFR-2 and enhances VEGF-A-induced VEGFR-2 signaling [ xref ]."
28835895
sparser
"Although these data support the role of NRP1 as a positive modulator of VEGF-A signalling, the fact that VEGF-A binding to NRP1 is dispensable for vascular permeability in vivo and that combining anti-NRP1 with anti-VEGF-A blocking antibodies has a synergistic effect on tumour angiogenesis and growth, suggests that NRP1 also promotes VEGF-A independent signalling [ xref ]."
32911833
reach
"In this report, we highlighted that tube formation may be also destructed independently of phactr-1 down-expression through the inhibition of VEGF-A 165 binding to both NRP-1 and VEGF-R1 using peptide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26362351
sparser
"In agreement with these biochemical data, we recently used the hindbrain model to show that VEGF121 is not able to bind NRP1 at detectable levels in vivo ( xref )."
26222953
sparser
"NRP1 binds VEGF-A via the b1 and b2 domains [ xref ] ( xref )."
32911833
sparser
"At a minimum, the identified compounds share a 2(1H)-pyridone core, and those with ‘pyridone and pyrimidone cores’ inhibited VEGF-A-NRP-1 binding with higher efficiency than EG00229; and as efficient as the SARS-CoV-2 S glycoprotein association with NRP-1."
33815686
reach
"In the NRP1-VEGF-A complex, NRP1 residues exhibit limited fluctuation, with overall RMSF below 3 Å; with regions spanning residues 280–285, 310–312, 375–380 and the loop III region (345–354) showing slightly higher RMSF relative to other regions of the protein (Figure 2A)."
34722943
reach
"It exhibits submicromolar potency in inhibition of VEGF-A binding to NRP1 and good functional inhibition of VEGF driven angiogenesis, cell migration, tumor invasiveness, and notably Treg cell activation."
29648813
sparser
"The basis for specific Nrp1-VEGF-A interactions in hemangiogenesis has been described biochemically and structurally ( xref , xref ), and other family members are actively being pursued."
23116416
reach
"As a second approach, we treated with EG00229, an inhibitor of VEGF-A and NRP -1 interaction."
30456845
reach
"17 Novel drug compounds which act as NRP1 antagonists could therefore exhibit their anticancer effects in three different ways : blocking tumor angiogenesis by blocking the NRP1 and VEGF-A interaction, 18 preventing tumor cell migration by binding to NRP1, 19 and reducing Treg or macrophage mediated suppression of the immune response."
29648813
sparser
"This observation has been proposed to be due to defective VEGF-A binding to NRP1 on outflow tract endothelium [ xref ], agreeing with the observation that Vegfa 120/120 mice lacking NRP1-binding VEGF165 have similar defects [ xref ]."
24521511
reach
"In contrast, endogenous Sema3F functions as a potent inhibitor of VEGF-A binding to Nrp1."
24079887
sparser
"Furthermore, treatment with anti-NRP1 blocking antibodies preventing NRP1 binding to VEGF-A, partially decreases VEGF-A-induced EC proliferation and AKT, ERK1/2 and p38 MAPK phosphorylation compared to treatment with an anti-VEGF-A antibody which completely abrogated these VEGF-A-induced responses [ xref ] ( xref )."
32911833
reach
"VEGF-A binds to its receptors VEGFR1 (Flt-1), VEGFR2 (Flk-1), and coreceptors neuropilin 1 and 2."
24963322
sparser
"Within the VEGF family, NRP1 binds VEGF-A, -B, -E and placenta growth factor (PlGF2), whereas NRP2 binds VEGF-A, -C, -D, and PlGF2 ( xref ; xref )."
25087623
reach
"EG00229 inhibited VEGF-A binding to NRP-1, decreased VEGFR-2 phosphorylation and the migration of lung carcinoma cells in vitro."
26090340
reach
"We show that charge reversal produces a decrease in Nrp1 binding to VEGF-A indicating a direct contribution to ligand binding selectivity."
23145112
reach
"Angiogenesis is believed to be influenced by NRP1 binding with VEGF-A, VEGF-B, VEGF-E, PlGF, and HGF/SF [3]."
34698182
reach
"VEGF-A 165 but not VEGF-A 121, also binds with neuropilin-1 and -2 (NRP-1 and NRP-2), which have been identified in endothelial cells."
22622803
sparser
"This is not the case with NRP-1, where the strong interaction between NRP-1 and VEGF-A is ensured by Glu154 and results in strong and selective binding of VEGF-A to NRP-1."
33815686
reach
"VEGF-A 165 binding to NRP1 is required for FAK signaling."
21653826
sparser
"However, loss of VEGF-A binding to NRP1 does not affect embryonic viability, which depends on a properly remodeled outflow tract [ xref ], and mice lacking semaphorin signaling through NRP1 also have defective outflow tract remodeling [ xref ]."
24521511
reach
"Nrp1 specifically binds the VEGF-A 164/5 isoform, which is essential for developmental angiogenesis."
23145112
reach
"Treatment of mice in utero with an antibody that blocks Sema3A binding to Nrp-1, but not with an antibody that blocks VEGF-A binding to Nrp-1, resulted in reduced lymphatic vessel function, abnormal morphology of the collecting lymphatic vessels and valves, and aberrant SMC coverage of lymphatic vessels."
22723300
sparser
"Nrp1 binds VEGFA and B via discrete domains in the core protein to promote tumor angiogenesis and progression [ xref ]."
24755488
reach
"No information on the spontaneous mutations of the amino-acid residues in the CendR binding pocket of NRP1 could also be found.Disrupting the key protein-protein interactions between NRP1 and VEGF-A at the b1 CendR binding site has long been the focus of drug discovery efforts, particularly for cancer therapy."
35215277
reach
"VEGF-A 165 binding to NRP1 is required for complex formation between NRP1 and KDR."
21653826
reach
"Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells."
20151671
reach
"VEGF-A binding to NRP might be due to the exon 8 C-terminus KPR motif, which inserts into a negative cleft in the NRP b1 domain (XREF_FIG) [XREF_BIBR, XREF_BIBR]."
18625544
sparser
"Selective ablation of Nrp1 in endothelial cells leads to angiogenic sprouting defects ( xref ) that occur independently of semaphorins ( xref ), suggesting that impaired Nrp1 binding to Vegfa is the primary defect."
26586223
reach
"In addition, the binding of VEGF-A (165) to NRP-1 potentiates its capacity to promote PGI (2) synthesis."
15637071
reach
"Additionally, mice lacking Nrp1, which is also as a Vegf receptor, and Nrp1-binding Vegfa isoforms have defects in both RGC projections and vascular structures, indicating additional functions of the Vegf pathway [189]."
33782712
sparser
"Based on the findings presented in this manuscript, we propose that VEGF-A binds to NRP-1 and that this complex is coupled to α6/β4-integrin by a GIPC1 homodimer as indicated in xref ."
29755126
reach
"VEGF-A 121 could bind to NRP1, with lower affinity than VEGF-A 165 [XREF_BIBR]."
28835895
reach
"VEGF-A, VEGF-B, VEGF-E and PlGF bind to neuropilin-1, which then associates with either VEGFR-1 or VEGFR-2."
21732275
sparser
"VEGF-A binding to NRP1 induced the interaction between GIPC1 and Syx, thereby promoting DJM-1 proliferation."
26209534
biogrid
No evidence text available
22318724
sparser
"Differently from semaphorins, VEGF-A binds exclusively to the NRP-1 coagulation factors domain ( xref )."
26090340
reach
"The finding that expression of the Y297A and D320A NRP1 mutants reduced high-affinity VEGF-A 165 binding to endothelial cells and VEGF-A 165 stimulation of endothelial cell migration and tubulogenesis in a coculture model provides strong evidence that VEGF-A 165 binding to NRP1 plays an important role in migratory responses important for angiogenesis."
21653826
reach
"Structural basis for selective vascular endothelial growth factor-A (VEGF-A) binding to neuropilin-1."
22318724
sparser
"Cell-cell communication analysis identified several important receptor-ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa)."
37100790
sparser
"Thus, three of the synthetic compounds significantly inhibited the interaction between VEGF-A and NRP-1, confirming that they compete for binding to the CendR site ( xref )."
32995772
sparser
"sNRP-1 inhibition of VEGF-A-NRP1 interaction was found to result in tumor cell death (Prud'homme & Glinka 2012)."
| DOI
reach
"In addition to binding to the VEGF TK receptors, VEGF-A isoforms featuring exon 7 also bind to the single pass transmembrane receptors Neuropilin 1 (NRP1) and NRP2."
33478167
reach
"VEGF-A binds to VEGFR-1, -2, and Neuropilin-1, and all of them are selectively though not exclusively expressed on vascular endothelium [XREF_BIBR]."
24288566
sparser
"These findings identified the NRP1-VEGF-A signaling axis for therapeutic targeting of chronic pain."
36729125
biogrid
No evidence text available
18325345
reach
"This lack of an embryonic vascular phenotype mirrors the result in mice with deficient VEGF-A binding to Nrp1 22."
28835631
reach
"These results mean that down-modulation of phactr-1 expression is not solely due to the VEGF-A 165 binding to NRP-1 and/or VEGF-R1."
26362351
sparser
"VEGFR-1 (also known as Flt1 ) is considered to be a decoy receptor that limits VEGF-A availability for VEGFR-2 and therefore activation and signaling of the VEGF-A/VEGFR-2 axis (decoy - or - sink hypothesis). xref , xref VEGF-A also binds to semaphorin receptor NRP1, xref a single spanning non–tyrosine kinase transmembrane protein that functions as a VEGFR-2 co-receptor."
30557701
sparser
"It is reported that Asp320 is very important for NRP1 to interact with different ligands and VEGF-A xref , xref , as well as for the CendR region in HTLV-1 18,22,23 and the SARS-CoV-2 xref , which is present in the analyzed interactions."
| PMC
sparser
"NRP1 binds to the VEGF-A HS binding domain primarily at R165 and secondarily at K147, E152 and E155 ( xref ), i.e., to a surface opposite that of HS ( xref )."
22897854
sparser
"In a mouse model of skin tumor, tumor-derived VEGF-A is involved in establishing a perivascular niche, in which a VEGF-A–Nrp1 autocrine loop promotes stemness and tumor progression [ xref ]."
33634866
reach
"Although sensory neurons and glia contribute to the expression of multiple VEGF-A isoforms, the nerve associated endothelial cells might potentially be exposed to higher levels of Nrp1 binding VEGF-A."
23395391
reach
"Correspondingly, all molecular descriptors were calculated for these compounds and they were considered part of the small molecule set.Since one objective of inhibiting the VEGF-A/NRP-1 interaction is disruption of pain signals, the full therapeutic effect will require drug exposure in the central nervous system (CNS)."
32995772
sparser
"VEGF-A binds to neuropilin 1 (NRP1), which is a VEGFR2 co-receptor [ xref ]."
35882297
reach
"VEGFA binding to both VEGFR2 and NRP1 on the same endothelial cell forms a cis NRP1, VEGFA, and VEGFR2 complex; the stoichiometry is likely two VEGFR2s, two NRP1s and one VEGFA."
30357843
sparser
"Similarly, the absence of the expression of VEGFR1 and VEGFR2 in skin and prostate cancer cells as well glioblastoma supports the model according to which VEGFA binding to NRP1 induces Rho signal activation [ xref ]."
32377503
reach
"VEGF-A binds to neuropilin 1 (NRP1), which is a VEGFR2 co-receptor [86]."
35882297
sparser
"The binding of VEGF-A to NRP1 enhances its affinity for VEGFR2 ( xref )."
25087623
reach
"Inhibition or knockdown of NRP-1, GIPC1 or Syx attenuates RhoA and p38 activity to reduce the ECS cell phenotype, and NRP-1 knockout, or pharmacologic inhibition of VEGF-A and NRP -1 interaction or RhoA activity, reduces p38 MAPK activity and tumor growth."
30456845
sparser
"In an in-silico screening of ∼480K small molecules binding to the extracellular b1b2 pocket of NRP1, we identified nine chemical series, with six compounds disrupting VEGF-A binding to NRP1."
36729125
reach
"In comparison, EG00229 inhibited the NRP-1/VEGF-A interaction with an IC value of 930 nM in our cell-free assay (Figure 6B)."
33787218
reach
"Consistent with this, blocking VEGF-A binding to Nrp1 with a monoclonal antibody impairs vascular remodeling in the peri-natal mouse retina 24."
28835631
reach
"VEGFA and VEGFC can interact with NRP1 and NRP2 and, as described above, VEGFA and NRP1 and VEGFC and NRP2 stimulate autocrine loops in ccRCC cells."
33461580
reach
"We coated plates with the extracellular domain of human NRP-1 (containing the a1a2 and the b1b2 regions) and added a selection of our compounds (based on SAR and commercial availability) to disrupt the NRP-1/VEGF-A interaction."
33787218
reach
"Sema3F functions with neuropilin-2 in axon guidance, but functionally blocks VEGF-A binding to neuropilin-1 to block angiogenesis."
20387901
sparser
"Since, both the spike protein of SARS-COV-2 and vascular endothelial growth factor-A (VEGF-A) bind to NRP-1, they tested weather VEGF-A/NRP-1 signaling was blocked by spike protein."
| PMC
sparser
"We next determined whether IDB0076 can bind to VEGFA and NRP1 simultaneously in the sandwich ELISA (dual-targeting ELISA)."
32560565
hprd
No evidence text available
16763549
bel
"Neuropilin-2 binds to VEGFR1, while neuropilin-1 binds to VEGF-165 and increases its affinity for VEGFR2 by approximately one order of magnitude"
15178810
reach
"This is not the case with NRP-1, where the strong interaction between NRP-1 and VEGF-A is ensured by Glu154 and results in strong and selective binding of VEGF-A to NRP-1."
33815686
reach
"Considering that the interaction of S1 CendR peptide with NRP-1 mimics that of its endogenous partner VEGF-A 164, the possible basis of differential binding of VEGF-A to NRP-1 and NRP-2 could be relevant to that of S1 to the two NRP isoforms."
33815686
sparser
"NRP1 has also been implicated in tumor growth and angiogenesis; inhibition by a blocking antibody that prevents VEGF-A binding to NRP1 enhanced the antitumor effects of the inhibitory anti-VEGF-A antibody, bevacizumab, in mouse xenograft models.( xref ) As an alternative to biological therapeutics, small molecule inhibitors of NRP1 function would be desirable, but development of protein−protein interaction inhibitors is not a trivial task. xref , xref We utilized the bicyclic peptide 1 , corresponding to the C-terminal 28 amino acids of VEGF-A 165 (Figure xref ) as a starting point for small molecule design."
20151671
sparser
"NRP-1 can associate and form a complex with VEGFR2 [ xref ], resulting in enhanced VEGF-A 165 induced VEGFR2 signalling, which was assumed to be mediated by VEGF-A 165 binding to NRP-1."
17979880
reach
"Sema3A directs a subset of neuronal growth cones as well as blood vessel growth by repulsion; when bound to Nrp-1, VEGF-A mediates vascular permeability and angiogenesis."
36997325
sparser
"VEGFA binds to Nrp1 as well and further activated VEGFR2."
36203599
reach
"When VEGF-A binds to NRP1, it facilitates the interaction of NRP1 with GIPC1, a scaffold protein."
29659486
sparser
"Although the relevance of this phenomenon in other retroviral infections remains to be studied, a similar mechanism driven by the interaction between NRP-1 and either VEGFA 165 or Env itself might be envisaged with HTLV-1."
21114861
reach
"However, loss of VEGF-A binding to NRP1 does not affect embryonic viability, which depends on a properly remodeled outflow tract [XREF_BIBR], and mice lacking semaphorin signaling through NRP1 also have defective outflow tract remodeling [XREF_BIBR]."
24521511
sparser
"This conclusion is consistent with the finding that NRP1-directed antibody, which selectively blocks VEGF-A 165 binding to NRP1 and inhibits VEGF-A 165 –induced endothelial cell migration, had little effect on KDR or ERK activation in HUVECs ( xref )."
21653826
reach
"Compound E is ChemBridge identifier 7739526 from ref 69, and compound F is "NRPa-308" from ref 70.Identification of nanomolar inhibitors of the NRP-1/VEGF-A interaction."
33787218
reach
"Compound 2 exhibited a biological profile consistent with inhibition of VEGF-A binding to NRP1 demonstrating an impairment, but not complete inhibition, of cell migration and VEGFR2 phosphorylation."
20151671
sparser
"This is not the case with NRP-1, where the strong interaction between NRP-1 and VEGF-A is ensured by Glu154 and results in strong and selective binding of VEGF-A to NRP-1."
| DOI
sparser
"We hypothesized that Sema3-Nrp1 and Vegf-Nrp1 interactions are important pathways in the orchestration of pulmonary vascular development during alveolarization."
23713442
reach
"Blockade of VEGF-A binding to NRP-1 with specific peptides and peptidomimetics."
26090340
sparser
"A triple mutant b1 protein (S346A, E348A, T349A) was previously shown to prevent VEGF-A binding to rat NRP1.( xref )"
20151671
sparser
"Interestingly, C-end rule peptides with a C-terminal arginine residue in a configuration similar to that of VEGF-A bind NRP1 to induce vascular permeability [ xref ], and this property may be exploited to enhance tumor penetration of chemotherapeutic drugs [ xref ]."
24521511
sparser
"In agreement, both the loss of NRP1 binding VEGF-A isoforms and, inversely, the loss of VEGF-A binding to NRP1 impair arterial development in the retina and the heart in a similar manner [ xref , xref ]."
24521511
reach
"VEGF-A 165 binding to NRP1 and NRP2 is important for migration of endothelial cells."
21653826
sparser
"Disrupting the key protein-protein interactions between NRP1 and VEGF-A at the b1 CendR binding site has long been the focus of drug discovery efforts, particularly for cancer therapy."
35215277
sparser
"Collectively, our findings show that NRP1-4 is a first-in-class compound targeting the NRP1-VEGF-A signaling axis to control voltage-gated ion channel function, synaptic activity, and curb chronic pain."
36729125
reach
"VEGF-A , a VEGF isoform, binds also to the co-receptor neuropilin-1."
28235425
reach
"In addition to Sema3, Nrp1 and Nrp2 also bind to vascular endothelial growth factor-A (VEGF-A) and -C (VEGF-C) family members respectively and function as their co-receptors."
27439112
sparser
"In this article, we have identified residues essential for VEGF-A 165 binding to NRP1, which constitute part of the putative binding pocket for VEGF-A 165 in the NRP1 b1 domain, defined by computational analysis of the b1 domain structure, and inferred from the crystal structure of the b1 domain."
21653826
reach
"10 VEGF-A, VEGF-B and PlGF-2 also bind to the semaphorin receptor neuropilin-1 with high affinity."
16616187
reach
"In vivo disruption of VEGF-A binding to Nrp1 has previously been shown to disturb blood vessel growth and patterning of the mouse retina XREF_BIBR, XREF_BIBR."
28835631
hprd
No evidence text available
11986311
sparser
"Moreover, phactr-1 down-expression is not limited to a peptide sequence able to specifically inhibit VEGF-A 165 binding to NRP-1 but is at least restrictive to a peptide sequence that inhibits VEGF-A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26362351
reach
"Spike inhibited viral activity by ∼35%, while the known NRP-1 inhibitor EG00229 was ineffective in this assay.Initial inspection of docking scores (Table 1) reveals no clear correlation between structural subtype and extent of the inhibition of NRP-1/VEGF-A interaction."
33787218
reach
"Correspondingly, all molecular descriptors were calculated for these compounds and they were considered part of the small molecule set.Since one objective of inhibiting the VEGF-A/NRP-1 interaction is disruption of pain signals, the full therapeutic effect will require drug exposure in the central nervous system (CNS)."
33787218
sparser
"It is reported the crystallographic structure of the interaction between NRP1 with EG00229 (PDB:3I97); which is demonstrating that the main amino acids important are: Thr316, Asp320, Ser346, Thr349 and Tyr353 in NRP1 to interact with EG00229, in which the same corresponding amino acids are identified when NRP1 interacts with VEGF-A 33."
| PMC
biogrid
No evidence text available
9529250
sparser
"Main effects results compared with APOE -ε4 interaction results showed that VEGFA and NRP1 expression are not associated with global cognition unless the APOE -ε4 allele is taken into account."
31791659
sparser
"Conversely, blocking NRP1 binding to VEGF-A with anti-NRP1 blocking antibodies abrogating VEGF-A binding to NRP1 but not to VEGFR2, reduces VEGF-induced EC migration, proliferation, vessel sprouting and neovascularisation in the eye, although to a lesser extent compared to VEGF blocking antibodies [ xref ]."
32911833
sparser
"Interaction between NRP and VEGF-A 165 -HBD was also observed in affinity chromatography protocols where His 6 -tagged NRP1 b1 domain that was bound to the Ni-NTA column was used to capture un-tagged VEGF-A 165 -HBD from the solution; the two proteins co-eluted upon addition of the imidazole."
23409021
reach
"VEGFA binds NRP1, which forms a complex with KDR on endothelial cells to initiate intracellular signaling associated with the proliferation, migration, and survival of endothelial cells."
31791659
reach
"Heparin binding VEGF-A or PlGF can also bind to neuropilin 1 (NRP-1) which increases their binding affinity to VEGF-R2 but these molecules can also bind NRP-1 independent of VEGF-R2 activation."
30849371
reach
"These results suggest that cooperative binding of VEGF-A to KDR and NRP-1 enhances KDR phosphorylation and its biological activities."
11968003
reach
"In agreement, both the loss of NRP1 binding VEGF-A isoforms and, inversely, the loss of VEGF-A binding to NRP1 impair arterial development in the retina and the heart in a similar manner [XREF_BIBR, XREF_BIBR]."
24521511
sparser
"In contrast, AdY297A NRP1 or AdD320A NRP1 decreased 125 I-VEGF-A 165 binding, the degree of inhibition increasing with increasing MOI, reaching ∼45 and 27% inhibition at the highest MOI tested for AdY297A NRP1 and AdD320A NRP1, respectively ( xref )."
21653826
reach
"Within the VEGF family, NRP1 binds VEGF-A, -B, -E and placenta growth factor (PlGF2), whereas NRP2 binds VEGF-A, -C, -D, and PlGF2."
25087623
reach
"Notably, compound 17, in the series of esters of 3,4-dihydroxycinnamic acid, showed a robust disruption of the VEGF-A/NRP-1 interaction (IC = 2.1 nM)."
33787218
reach
"While three receptors- VEGF-R1 (Flt-1), VEGFR2 (Flk-1) and neuropilin-1 bind VEGF-A, VEGFR2 signaling is considered crucial to vascular formation."
20434959
sparser
"Though TKPR has been reported to disrupt the NRP1-VEGF interface ( xref ), the results of the present study cannot conclusively support that finding given the inconsistency of binding affinity scores across the three simulations of NRP1-TKPR (-23.67 ± 11.80 kcal/mol, -67.33 ± 5.31 kcal/mol, -51.48 ± 19.13 kcal/mol) and NRP1-VEGF-A (-85.81 ± 18.66 kcal/mol, -67.34 ± 11.27 kcal/mol, -82.07 ± 18.59 kcal/mol)."
34722943
reach
"As VEGF-A binds to NRP-1, it increases the interaction between NRP-1 and GIPC1 (a scaffold protein) and facilitates the assembly of the GAIP/RGS19-interacting protein (GIPC1) + Syx signaling molecular complex, resulting in RhoA GTP binding."
35534753
reach
"Structure activity relationship study of tetrapeptide inhibitors of the Vascular Endothelial Growth Factor A binding to Neuropilin-1."
28627371
reach
"As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling."
33009246
reach
"Nrp-1 can bind VEGF-A 165, VEGF-B, VEGF-E, and placental growth factor (PIGF)."
30197476
reach
"Thus, five of the synthetic and one of the natural compounds significantly inhibited the interaction between VEGF-A and NRP-1, confirming that they compete for binding to the CendR site (Table 1)."
33787218
reach
"(A) Representative concentration curves for inhibition of the NRP-1/VEGF-A interaction assessed by ELISA (see Methods for details)."
33787218
sparser
"However, antiangiogenic VEGFA cannot bind NRP1."
26562337
reach
"Nrp-1 also binds with high affinity to VEGFR-1, which counteracts an interaction of VEGF-A and Nrp-1 and finally results in reduced VEGF-A effectiveness [XREF_BIBR]."
23475067
reach
"NRP1 was first identified as a semaphorin 3A receptor, but can also bind the VEGF-A 165 isoform of VEGF-A with high affinity."
23639442
reach
"VEGF-A binds VEGFR1 and VEGFR2 homodimers, VEGFR1/2 and VEGFR2/3 heterodimers, as well as Nrp1 homodimers; VEGF-B and PGF bind VEGFR1 homodimers, VEGFR1/2 heterodimers and Nrp1 homodimers; and VEGF-C and VEGF-D bind VEGFR2 and VEGFR3 homodimers, VEGFR2/3 heterodimers and Nrp2 homodimers."
25662260
sparser
"To clarify the nature of these interaction results on cross-sectional cognition, stratified analyses showed that in APOE -ε4 carriers, higher expression of NRP1 (β=−0.176, p=0.034) and VEGFA (β=−0.027, p=0.019) were associated with worse global cognition scores; whereas in APOE -ε4 non-carriers, higher NRP1 (β=0.112, p=0.003) expression predicted better global cognition scores."
31791659
sparser
"To clarify the correlation between the interaction of VEGF-A and its receptor NRP-1, and cell growth inhibition by troglitazone, PC-14 cells were used for the following experiment."
20214829
reach
"To assay the inhibitory potency of Nrp1 and Nrp2, we tested the ability of Nrp1 and Nrp2 to inhibit VEGF-A binding to Nrp1 affinity plates in a dose dependent manner (XREF_FIG)."
23145112
reach
"Thus, all the isoforms can bind the two main VEGFA tyrosine kinase receptors, VEGFR1 (FLT1) and VEGFR2 (KDR, previously also known as FLK1), while NRP1 binds with higher affinity the larger VEGFA isoforms, such as VEGFA165 and VEGFA189, compared to VEGFA121 by interacting with the heparin binding domain encoded by exon 7, even though the interaction between VEGFA and NRP1 also involves the exon 8 encoded epitope, which is common to all the isoforms [58,59,60,61]."
33947161
reach
"NRP1 and NRP2, originally discovered as neuronal receptors for semaphorins, bind the most common splice-variant of VEGF-A (VEGF ) and form a complex with VEGFR-2 and VEGFR-1 to regulate their signalling (Fuh et al., 2000)."
24859987
sparser
"According to the literature data, the heptapeptide A7R is known to be an effective antagonist of the VEGF-A 165 binding with NRP-1 and to show in vivo anti-angiogenic properties [ xref ], whereas the Lys(hArg)-Dab-Pro-Arg peptidomimetic is much more active (IC 50 = 0.2 μM) than the heptapeptide A7R (IC 50 = 5.9 μM [ xref ]), with a stability half-life in human serum that is nearly 2 days [ xref , xref ]."
35056995
sparser
"Compound 2 exhibited a biological profile consistent with inhibition of VEGF-A binding to NRP1 demonstrating an impairment, but not complete inhibition, of cell migration and VEGFR2 phosphorylation."
20151671
reach
"It has been proposed that both VEGF-A 165 and VEGF-A 121 can bind NRP1; however, only VEGF-A 165 is believed to form a heteromeric complex with VEGFR2 and NRP1."
27044325
sparser
"In contrast, a study in chick revealed that VEGFR2 and Nrp1 are expressed in cranial NCCs while VEGF-A is expressed in the surface ectoderm adjacent to the rhombomere 4 NCC migratory route, and furthermore, that the VEGF-A-Nrp1 interaction was required for proper cranial NCC invasion from the rhombomere 4 migratory stream into branchial arch 2 ( xref )."
25662260
sparser
"In this cascade, VEGF-A forms a complex with NRP-1, α6/β4-integrin, GIPC1 and TG2 to trigger signaling events that activate YAP1/ΔNp63α signaling."
30693974
sparser
"A recent clinical study has linked the genetic interaction of NRP1 and VEGFA with APOE-ε4 in the process of cognition [ xref ]."
32911833
reach
"We next tested the selectivity of the most potent compounds by comparing their ability to inhibit Nrp2/VEGF-C interactions with Nrp1/VEGF-A interactions (Table 2)."
32344185
sparser
"Using a novel chimeric C-furSema, we demonstrate that combining a single C-terminal arginine with the helical motif is necessary and sufficient for potent inhibition of binding of VEGF-A to Nrp1."
24079887
sparser
"Mesangial cells targeted by this receptor-ligand interaction showed enrichment of genes in the signaling pathways of Rho GTPase small molecules, axon guidance, actin skeleton, VEGFA-NRP1 induced angiogenesis, and the endothelin-1 pathway."
36055599
sparser
"The results reveal the basis for the potent and selective binding of VEGF-A(164) to Nrp1."
22318724
sparser
"Thus, 2 was identified as a non-peptide antagonist of VEGF-A binding to NRP1."
20151671
reach
"In addition, the binding of VEGF-A and NRP-1 increased after VEGF 165 recombinant protein was re-added to the CM (XREF_FIG, bottom)."
27364975
reach
"To determine if VEGFA-binding neuropilin 1 was required for angiogenesis, transgenic mice that expressed a mutant neuropilin 1 with a point mutation in the VEGF-binding b1 domain (Nrp1 ) were generated along with littermate wild-type controls."
34956992
sparser
"As VEGF-A binds to NRP-1, it increases the interaction between NRP-1 and GIPC1 (a scaffold protein) and facilitates the assembly of the GAIP/RGS19-interacting protein (GIPC1) + Syx signaling molecular complex, resulting in RhoA GTP binding."
35534753
sparser
"Using an ELISA, we demonstrate that six compounds disrupt VEGF-A-NRP-1 binding more effectively than EG00229, a known NRP-1 inhibitor."
32995772
reach
"NRPa-308, discovered by its ability to inhibit VEGFA binding to NRP1 [XREF_BIBR], is a better NRP2 inhibitor."
33461580
reach
"Nrp1 binds VEGFA and B via discrete domains in the core protein to promote tumor angiogenesis and progression [XREF_BIBR]."
24755488
sparser
"Blockade of VEGF-A binding to NRP-1 with specific peptides and peptidomimetics."
26090340
reach
"Such a tool has major implication in sensitive diagnosis that shall allow physicians to evaluate patient response to treatment.More unpublished structures are recently deposited at PDB; some of them i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24139944
sparser
"We demonstrate that the exon 8-encoded C-terminal arginine is essential for the interaction of VEGF-A with Nrp1 and mediates high affinity Nrp binding."
22318724
sparser
"The suitability of the binding pocket to accommodate different ligands with the CendR terminals is evident from the comparison of the crystal complexes of VEGF-A 164 -NRP1 and SARS-CoV-2-NRP1 ( xref A), which show remarkable similarities in the binding mode of their CendR sequences."
35215277
sparser
"This could be explained by the fact that the NRP1/VEGFA-165 complexes are already assembled in a way that allows direct interactions with VEGFR2 without rearrangement."
29630862
reach
"EG00229, an inhibitor of VEGF-A and NRP -1 interaction, was obtained from R&D Systems (4931, Minneapolis, MN)."
30456845
reach
"Using a novel chimeric C-furSema, we demonstrate that combining a single C-terminal arginine with the helical motif is necessary and sufficient for potent inhibition of binding of VEGF-A to Nrp1."
24079887
reach
"In the NRP1-VEGFA complex, NRP1 residues exhibit limited fluctuation, with overall RMSF below 3 Å; with regions spanning residues 280-285, 310-312, 375-380 and the loop III region (345-354) showing slightly higher RMSF relative to other regions of the protein (Fig. 2A)."
34722943
reach
"Conversely, targeting NRP1 with specific monoclonal antibodies [20], small interfering RNAs [21], soluble NRP1 [21-24], NRP1 inhibiting peptides [21,25-28], and small molecular inhibitors of the NRP1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21338642
reach
"27 Herein, we utilize EG00229 as a starting point for the discovery of potent and bioavailable inhibitors of the NRP1 and VEGF-A interaction, resulting in the identification of 1 (EG013777) as a new lead."
29648813
sparser
"This might be partly attributed to significantly reduced NRP-1 binding by VEGF121 compared to VEGF165 [ xref ]."
34793603
sparser
"Figure 2: Root mean square fluctuation (RMSF) of protein Cα atoms obtained from three independent runs of the different peptides bound to NRP1. (A) NRP1 protein in the NRP1–VEGF-A complex; (B) VEGF-A ligand in the NRP1–VEGF-A complex; (C) NRP1 protein in the NRP1–S1 complex; (D) NRP1 protein in the NRP1–R complex; (E) NRP1 protein in the NRP1–HRG complex; (F) NRP1 protein in the NRP1–RRRR complex; (G) NRP1 protein in the NRP1–RRAK complex; (H) NRP1 protein in the NRP1–RRAR complex; (I) NRP1 protein in the NRP1–RRAH complex; (J) NRP1 protein in the NRP1–TKPR complex; (K) NRP1 protein in the NRP1–TKPPR complex; (L) NRP1 protein in the NRP1–PPR complex; (M) NRP1 protein in the NRP1–PPRV complex; (N) NRP1 protein in the NRP1–PPR(V) complex; (O) NRP1 protein in the NRP1–EG0029 complex; (P) NRP1 protein in the NRP1– RRAA complex; (Q) NRP1 protein in the NRP1–RAAR complex; (R) NRP1 protein in the NRP1–ARAR complex."
34722943
reach
"Nrp1 -/- hindbrains showed some defasciculation of these dorsolateral axons, but they were still clearly present in the mutant, suggesting that this are a suitable model to examine VEGFA isoform binding to NRP1."
25519242
sparser
"VEGF-A binding to the dimeric complex of its receptor VEGFR2 and co-receptor NRP-1 triggers phosphorylation of the VEGFR2 cytoplasmic domain at Y1175 ( xref )."
32995772
reach
"Hence, though VEGF-A interacts with both NRP-1 and NRP-2, it exhibits a fifty-fold greater affinity for NRP-1."
33815686
reach
"Nrp1 binds directly to VEGF-A with high affinity, but the nature of their selective binding has remained unclear."
22318724
sparser
"However, reduced extracellular binding of VEGF-A to Nrp1 is known to disrupt post-natal blood vessel development and growth."
28835631
reach
"It is notable that VEGF-A binds to both NRP-1 and NRP-2 but has higher affinity for NRP-1 due to amino acid substitutions within the first loop region of NRP-1 that provide additional contacts between NRP-1 Thr299 and VEGF-A Glu154 (Figure 1B,C)."
33787218
sparser
"For example, NRP1 predominantly binds to VEGF-A 165 to mediate angiogenesis [ xref , xref , xref ] in vascular ECs, whereas NRP2 interacts with VEGF-C to regulate lymphangiogenesis [ xref , xref , xref , xref ]."
32708258
reach
"XREF_BIBR Notably, a previous research has reported that peptides inhibiting the binding of VEGF-A and NRP -1 could inhibit breast cancer progression, XREF_BIBR and two groups have demonstrated that a monoclonal antibody targeting neuropilin-1 or a neuropilin-1 antagonist could exert anticancer effects in breast cancer via in vitro and in vivo experiments."
30214235
reach
"We evaluated the ability of hit compounds to interfere with the NRP-1/VEGF-A interaction using an enzyme linked immunosorbent assay (ELISA)."
33787218
reach
"Remarkably, mice harboring a Y297A mutation in the Nrp1 extracellular domain that specifically inhibits VEGF binding, but also causes Nrp1 hypomorphism, survive past birth demonstrating that VEGFA binding by Nrp1 is not required for a viable cardiovascular system."
26849476
reach
"Reduced binding of VEGF-A to Nrp1 has previously been shown to impair post-natal angiogenesis and arteriogenesis XREF_BIBR, XREF_BIBR."
28835631
reach
"Accordingly, the disruption of NRP1 or NRP2 binding to VEGF-A (165) or HGF with a blocking antibody, decreased the proliferation and migration of endothelial cells."
18065694
reach
"VEGF-A also binds to neuropilin 1 (NRP1), which presents VEGF-A to VEGFR-2 and enhances VEGF-A-induced VEGFR-2 signaling [XREF_BIBR]."
28835895
reach
"The library was tested for the ability to inhibit alkaline phosphatase (AP)-tagged VEGF-A binding to Nrp1 utilizing an in vitro plate binding assay."
23871893
sparser
"The above studies suggest that VEGF-A and NRP-1 may physically interact."
26804163
reach
"Consequently, disruption of the VEGF-A/NRP1 complex by the SARS-CoV-2 spike protein was found to impair pain signalling and reduce neuropathic pain, which may contribute to the asymptomatic COVID-19 infections and further spread of the virus [22]."
35215277
reach
"We found that 3 hit compounds blocked more than 50% of VEGF-A binding to NRP-1."
32995772
reach
"VEGF-A interacts with NRP-1 and this leads to enhanced VEGF-A interaction with VEGFR, leading to enhanced angiogenesis."
26804163
biogrid
No evidence text available
9529250
sparser
"Mutation of this region results in the largest net loss of VEGF-A binding to Nrp1, consistent with a direct interaction involving a hydrogen bond between Nrp1-T299 and VEGF-A-E154 xref ."
23145112
sparser
"A library of 5 × 10 5 compounds was screened for specifically targeting this site; nine chemical series were reported with lead- or drug-like physical and chemical properties, out of which six compounds effectively disrupted VEGF-A–NRP-1 interaction, and all nine inhibited VEGF-A triggered VEGFR2 phosphorylation."
34961486
reach
"For example, NRP1 predominantly binds to VEGF-A to mediate angiogenesis [56,57,58] in vascular ECs, whereas NRP2 interacts with VEGF-C to regulate lymphangiogenesis [46,59,60,61]."
32708258
reach
"Furthermore, they demonstrated that six of them inhibit VEGF-A/NRP-1 binding more effectively than EG00229, and two of them inhibit the entry and fusion into the host cell of the SARS-CoV-2 S protein [36,38]."
34202613
reach
"For example, VEGF-A binds to Flk-1 and coreceptor neuropilin-1 (NP-1), activating Notch signaling and promoting EphrinB2 expression, while suppressing EphB4; thus, establishing an arterial identity while suppressing a venous fate in endothelial cells."
27451101
reach
"More recently, Parker et al. [XREF_BIBR] reported on the crystal structure of VEGF-A bound to Nrp1."
22948112
reach
"NRP1 has also been implicated in tumor growth and angiogenesis; inhibition by a blocking antibody that prevents VEGF-A binding to NRP1 enhanced the antitumor effects of the inhibitory anti-VEGF-A antibody, bevacizumab, in mouse xenograft models."
20151671
sparser
"As shown in xref , AGuIX@PS@ KDKPPR displaces the binding of biotinylated VEGF-A 165 to NRP-1 (EC 50 =19 µM) more effectively than maleimido-PS@ KDKPPR and AGuIX@PS@scramble (81 and 176 µM, respectively)."
29026302
biogrid
No evidence text available
21939755
sparser
"M. W. Parker et al. reported the first detailed picture of the structural basis for the binding of NRP-1 and VEGF-A. The binding interface involved regions encoded by both exons 7 and 8 of VEGF-A. Exon 7 encoded residues primarily govern selectivity, whereas exon 8 encoded residues mainly mediate high-affinity binding [ xref ]."
| PMC
reach
"However, an anti-NRP-1 humanized antibody that hampers VEGF-A binding to NRP-1, even though well tolerated as single agent, showed modest clinical activity [XREF_BIBR]."
28977999
reach
"VEGF-A 165 binds to the co-receptor neuropilin 1 (NRP1) to form a VEGFR2/NRP1/VEGF-A 165 signalling complex."
25910937
reach
"However, the peptide extensions in VEGF-Ax generated by translational readthrough are significantly different in mice and humans (74% identity), particularly in the C-terminus that is required for VEGF-A binding to neuropilin-1, a VEGFR2 co-receptor."
26122849
sparser
"Using ELISA, we demonstrate that six compounds disrupt VEGF-A-NRP-1 binding more effectively than EG00229, a known NRP-1 inhibitor."
33787218
sparser
"Thus, five of the synthetic and one of the natural compounds significantly inhibited the interaction between VEGF-A and NRP-1, confirming that they compete for binding to the CendR site (Table 1)."
33787218
sparser
"Consistent with this, blocking VEGF-A binding to Nrp1 with a monoclonal antibody impairs vascular remodeling in the peri-natal mouse retina xref ."
28835631
reach
"VEGF-A binds to NRP1 and serves as a chemotactic factor for lung-resident NRP1 + ILC3, suggesting these cells may play a role in the initiation of ectopic pulmonary lymphoid aggregates in smokers and patients with chronic obstructive pulmonary disease [XREF_BIBR]."
30529190
reach
"The potency of compound 2 in inhibiting VEGF-A binding to NRP1 was thus very similar to that of the bicyclic peptide compound 1, which inhibits 125 I-VEGF-A binding to PAE and NRP1 and tumor cells with IC 50 values of 2-3 muM and inhibits 125 I-VEGF-A binding to HUVECs with an IC 50 of 20 muM."
20151671
sparser
"In agreement, abolishing VEGF-A binding to NRP1 in Nrp1 Y297A/Y297A mice ( xref ) recapitulated the vascular extension defect caused by endothelial NRP1 loss in the P6 retina ( xref E, red arrow)."
26051942
reach
"As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling."
32869019
sparser
"Our studies in ECS cells demonstrate that VEGF-A interacts with NRP-1 and that this interaction is required for cell survival, spheroid formation, invasion, and migration [ xref ]."
29755126
reach
"The most common splice isoform VEGF-A (165), subject of the present study, additionally interacts with neuropilin 1 and various cell-surface heparan sulfate proteoglycans to modulate the intracellular response."
25175707
reach
"Effects of Semaphorins and Neuropilin -1 17, however, involve a more complicated process and have been shown to function as pro - angiogenesis stimuli (VEGF-A 165 binding to NRP-1 and VEGFR-2 and Plexin-A1 or 2) or facilitate migration (Np-1/Np-2/VEGFR-1/Plexin-A1/2 when bound by VEGF-A (165, 145, 121), VEGF-B and PlGF-2)."
23208836
reach
"Since VEGF-A 121 binds Nrp1 but does cross-link it to VEGFR2, this result can be construed to suggest that Nrp1 can signal independently from VEGFR2."
22617029
sparser
"VEGF121 can also bind NRP1, but with 50-fold lower affinity than VEGF165, due to the absence of an exon 7-encoded domain that enhances binding [ xref ]."
23475065
sparser
"Our results reveal that C-furSema is able to inhibit binding of VEGF-A to neuropilin with an increase in potency of two to three orders of magnitude relative to previous inhibitors."
20387901
sparser
"Thus, all the isoforms can bind the two main VEGFA tyrosine kinase receptors, VEGFR1 (FLT1) and VEGFR2 (KDR, previously also known as FLK1), while NRP1 binds with higher affinity the larger VEGFA isoforms, such as VEGFA165 and VEGFA189, compared to VEGFA121 by interacting with the heparin binding domain encoded by exon 7, even though the interaction between VEGFA and NRP1 also involves the exon 8 encoded epitope, which is common to all the isoforms [58,59,60,61]."
33947161
reach
"VEGF-A 165 binds to NRP1 and NRP2, whereas VEGF-A 145 binds only to NRP2 [XREF_BIBR, XREF_BIBR]."
15693956
reach
"Compounds 16 and 17 displayed more than 60% inhibition and were more active than the EG00229 control (compound 21), a known antagonist that prevents VEGF-A binding to NRP1 and has also been shown to block spike protein binding to NRP1."
35215277
reach
"Our data further showed that expression of the Y297A NRP1 mutant prevented VEGF-A 165 -induced complex formation between NRP1 and KDR, indicating that VEGF-A 165 binding to NRP1 is essential for formation of NRP1 and KDR heterodimers either alone or as homodimers or oligomers with WT NRP1, and that these heterocomplexes may be rapidly destabilized by subsequent VEGF-A 165 binding to KDR."
21653826
reach
"Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling."
33009246
reach
"However, reduced extracellular binding of VEGF-A to Nrp1 is known to disrupt post-natal blood vessel development and growth."
28835631
sparser
"The addition of VEGFR2 EC-TM domains to the pre-formed NRP1/VEGFA-165 complexes does not change the self-association of NRP1."
29630862
sparser
"More recently, Parker et al. [ xref ] reported on the crystal structure of VEGF-A bound to Nrp1."
22948112
biogrid
No evidence text available
11986311
sparser
"In the present study we determined the basis for preferential Nrp1 binding to VEGF-A. Mutagenesis of residues surrounding the shared C-terminal arginine binding pocket identifies residues that differ between Nrp1 and Nrp2 and underlie the observed VEGF-A specificity."
23145112
bel
"VEGF supports the survival of primary motor neurons and a motor-like cell line in vitro and could protect these motor neurons from hypoxia-induced cell death by binding with neuropilin-1, a receptor known to be involved in axon guidance during development [42, 45]."
21861815
reach
"In the second experiment, EG00229 was tested in a spike-dependent assay for Disrupting the key protein-protein interactions between NRP1 and VEGF-A at the b1 CendR binding site has long been the focus of drug discovery efforts, particularly for cancer therapy."
35215277
sparser
"Disruption of VEGF-A binding to Nrp1 has previously been linked with reduced Nrp1 expression in various different mouse tissues xref ."
28835631
reach
"Mutational analysis of VEGF-A binding to NRP1 was therefore performed to confirm the identity of the binding pocket."
20151671
reach
"Conserved between both are the residues which form the C-terminal arginine binding pocket demonstrated to be essential for VEGF-A and Nrp binding XREF_BIBR (XREF_FIG, asterisk)."
23145112
reach
"Our finding that Y297A NRP1 reduces FAK phosphorylation at Tyr 407 suggests that VEGF-A 165 binding to NRP1 plays a key role in focal adhesion signaling important for cell migration."
21653826
reach
"Most recently, a VEGF-A receptor neuropilin 1 binding ligand (EG00229) was designed and synthesized that reduced the viability of A549 lung carcinoma cells XREF_BIBR."
22916091
reach
"Notably, compound 17, in the series of esters of 3,4-dihydroxycinnamic acid, showed a robust disruption of the VEGF-A/NRP-1 interaction (IC 50 = 2.1 nM)."
33787218
sparser
"Nrp2 and Nrp1 Chimera Relieve C-furSema Mediated Inhibition of AP-VEGF-A Binding to Nrp1."
23145112
reach
"Initial studies showed that VEGF-A binding to VEGFR-2 and NRP1 or NRP2 receptor complexes promoted endothelial cell proliferation, migration, and tube formation in vitro as well as angiogenesis in vivo."
25285016