Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1

2016 ◽  
Vol 26 (12) ◽  
pp. 2843-2846 ◽  
Author(s):  
Karolina Grabowska ◽  
Anna K. Puszko ◽  
Piotr F.J. Lipiński ◽  
Anna K. Laskowska ◽  
Beata Wileńska ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cyclic Peptide ◽  
Biological Evaluation ◽  
Vascular Endothelial ◽  
Design Synthesis ◽  
Factor Binding ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

scholarly journals Vascular Endothelial Growth Factor Receptors in Human Mesangiumin Vitroand in Glomerular Disease

2000 ◽  
Vol 11 (7) ◽  
pp. 1236-1243 ◽  
Author(s):  
STEPHEN THOMAS ◽  
JOHANN VANUYSTEL ◽  
GABRIELLA GRUDEN ◽  
VERÓNICA RODRÍGUEZ ◽  
DAVINA BURT ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Ex Vivo ◽  
Fold Increase ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Glomerular Diseases ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

Abstract. Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptorsin vitroandex vivoand evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMCin vitroby immunofluorescence and Western blotting. VEGF165induced a dose-responsive increase in3H-thymidine incorporation (25 ng/ml VEGF165: 2.3-fold increase ; 50 ng/ml : 3.8-fold ; 100 ng/ml : 4.8-fold ; 200 ng/ml : 3.4-fold ;P= 0.016) and in cell number (50 ng/ml VEGF165: 1.2-fold increase ; 100 ng/ml : 1.6-fold ; 200 ng/ml : 1.4-fold ;P= 0.005), effects prevented by an anti-VEGF165polyclonal neutralizing antibody (100 μg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF165: 1.4-fold increase). Inex vivoexperiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF165induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.

Antiangiogenic and antitumor activities of peptide inhibiting the vascular endothelial growth factor binding to neuropilin-1

Life Sciences ◽  
2006 ◽  
Vol 79 (25) ◽  
pp. 2370-2381 ◽  
Author(s):  
Anna Starzec ◽  
Roger Vassy ◽  
Antoine Martin ◽  
Marc Lecouvey ◽  
Mélanie Di Benedetto ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Antitumor Activities ◽  
Factor Binding ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

scholarly journals Triazolopeptides Inhibiting the Interaction between Neuropilin-1 and Vascular Endothelial Growth Factor-165

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1756 ◽  
Author(s):  
Bartlomiej Fedorczyk ◽  
Piotr F. J. Lipiński ◽  
Anna K. Puszko ◽  
Dagmara Tymecka ◽  
Beata Wilenska ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Inhibitory Activity ◽  
General Structure ◽  
Peptide Bond ◽  
Vascular Endothelial ◽  
Present Contribution ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

Inhibiting the interaction of neuropilin-1 (NRP-1) with vascular endothelial growth factor (VEGF) has become an interesting mechanism for potential anticancer therapies. In our previous works, we have obtained several submicromolar inhibitors of this interaction, including branched pentapeptides of general structure Lys(Har)-Xxx-Xxx-Arg. With the intent to improve the proteolytic stability of our inhibitors, we turned our attention to 1,4-disubstituted 1,2,3-triazoles as peptide bond isosteres. In the present contribution, we report the synthesis of 23 novel triazolopeptides along with their inhibitory activity. The compounds were synthesized using typical peptide chemistry methods, but with a conversion of amine into azide completely on solid support. The inhibitory activity of the synthesized derivatives spans from 9.2% to 58.1% at 10 μM concentration (the best compound Lys(Har)-GlyΨ[Trl]GlyΨ[Trl]Arg, 3, IC50 = 8.39 μM). Synthesized peptidotriazoles were tested for stability in human plasma and showed remarkable resistance toward proteolysis, with half-life times far exceeding 48 h. In vitro cell survival test resulted in no significant impact on bone marrow derived murine cells 32D viability. By means of molecular dynamics, we were able to propose a binding mode for compound 3 and discuss the observed structure–activity relationships.

scholarly journals Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: synthesis, in vitro biological evaluation and molecular docking

MedChemComm ◽  
2018 ◽  
Vol 9 (6) ◽  
pp. 1054-1058
Author(s):  
Wuji Sun ◽  
Shubiao Fang ◽  
Hong Yan
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Cancer Therapy ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy.

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