scholarly journals Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction

2010 ◽  
Vol 53 (5) ◽  
pp. 2215-2226 ◽  
Author(s):  
Ashley Jarvis ◽  
Charles K. Allerston ◽  
Haiyan Jia ◽  
Birger Herzog ◽  
Acely Garza-Garcia ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

scholarly journals Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood–retinal barrier dysfunction

2012 ◽  
Vol 446 (3) ◽  
pp. 455-467 ◽  
Author(s):  
Paul M. Titchenell ◽  
Cheng-Mao Lin ◽  
Jason M. Keil ◽  
Jeffrey M. Sundstrom ◽  
Charles D. Smith ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Endothelial Permeability ◽  
Kinase Assay ◽  
Vascular Endothelial ◽  
Blood Retinal Barrier ◽  
Atypical Pkc ◽  
Endothelial Growth Factor

Pro-inflammatory cytokines and growth factors such as VEGF (vascular endothelial growth factor) contribute to the loss of the BRB (blood–retinal barrier) and subsequent macular oedema in various retinal pathologies. VEGF signalling requires PKCβ [conventional PKC (protein kinase C)] activity; however, PKCβ inhibition only partially prevents VEGF-induced endothelial permeability and does not affect pro-inflammatory cytokine-induced permeability, suggesting the involvement of alternative signalling pathways. In the present study, we provide evidence for the involvement of aPKC (atypical PKC) signalling in VEGF-induced endothelial permeability and identify a novel class of inhibitors of aPKC that prevent BRB breakdown in vivo. Genetic and pharmacological manipulations of aPKC isoforms were used to assess their contribution to endothelial permeability in culture. A chemical library was screened using an in vitro kinase assay to identify novel small-molecule inhibitors, and further medicinal chemistry was performed to delineate a novel pharmacophore. We demonstrate that aPKC isoforms are both sufficient and required for VEGF-induced endothelial permeability. Furthermore, these specific, potent, non-competitive, small-molecule inhibitors prevented VEGF-induced tight junction internalization and retinal endothelial permeability in response to VEGF in both primary culture and in rodent retina. The results of the present study suggest that aPKC inhibition with 2-amino-4-phenyl-thiophene derivatives may be developed to preserve the BRB in retinal diseases such as diabetic retinopathy or uveitis, and the BBB (blood–brain barrier) in the presence of brain tumours.

scholarly journals Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity

2000 ◽  
Vol 97 (6) ◽  
pp. 2573-2578 ◽  
Author(s):  
M. L. Gagnon ◽  
D. R. Bielenberg ◽  
Z.'e. Gechtman ◽  
H.-Q. Miao ◽  
S. Takashima ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
In Vivo Expression ◽  
Endothelial Growth Factor

scholarly journals Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma

Cancer ◽  
2001 ◽  
Vol 94 (1) ◽  
pp. 258-263 ◽  
Author(s):  
Mitra Fakhari ◽  
Dieter Pullirsch ◽  
Dietmar Abraham ◽  
Kurosh Paya ◽  
Reinhold Hofbauer ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptors ◽  
Vascular Endothelial ◽  
Human Neuroblastoma ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

AAL881, a Novel Small Molecule Inhibitor of RAF and Vascular Endothelial Growth Factor Receptor Activities, Blocks the Growth of Malignant Glioma

2006 ◽  
Vol 66 (17) ◽  
pp. 8722-8730 ◽  
Author(s):  
Sith Sathornsumetee ◽  
Anita B. Hjelmeland ◽  
Stephen T. Keir ◽  
Roger E. McLendon ◽  
David Batt ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Malignant Glioma ◽  
Small Molecule ◽  
Growth Factor Receptor ◽  
Small Molecule Inhibitor ◽  
Vascular Endothelial ◽  
Molecule Inhibitor ◽  
Endothelial Growth Factor

scholarly journals αvβ3 Integrin Limits the Contribution of Neuropilin-1 to Vascular Endothelial Growth Factor-induced Angiogenesis

2009 ◽  
Vol 284 (49) ◽  
pp. 33966-33981 ◽  
Author(s):  
Stephen D. Robinson ◽  
Louise E. Reynolds ◽  
Vassiliki Kostourou ◽  
Andrew R. Reynolds ◽  
Rita Graça da Silva ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Αvβ3 Integrin ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo–maternal interface

2011 ◽  
Vol 154 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Dunja M. Baston-Buest ◽  
Anne C. Porn ◽  
Andrea Schanz ◽  
Jan-S. Kruessel ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Human Embryo ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor
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