کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2116210 | 1084779 | 2014 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model](/preview/png/2116210.png)
Neuropilin-1/-2 (+33 NRPs), VEGF-A165 co-receptors, are over-expressed during cancer progression. Thus, NRPs targeted drug development is challenged using a multistep in silico/in vitro screening procedure. The first fully non-peptidic VEGF-A165/NRPs protein–protein interaction antagonist (IC50 = 34 μM) without effect on pro-angiogenic kinases has been identified (compound-1). This hit showed breast cancer cells anti-proliferative activity (IC50 = 0.60 μM). Compound-1 treated NOG-xenografted mice significantly exerted tumor growth inhibition, which is correlated with Ki-67low expression and apoptosis. Furthermore, CD31+/CD34+ vessels are reduced in accordance with HUVEC-tube formation inhibition (IC50 = 0.20 μM). Taking together, compound-1 is the first fully organic inhibitor targeting NRPs.
Journal: Cancer Letters - Volume 349, Issue 2, 28 July 2014, Pages 120–127