基于微孔板筛选神经纤毛蛋白-2/血管内皮生长因子-C相互作用的小分子抑制剂。
Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions.
作者信息
Parker Matthew W, Vander Kooi Craig W
机构信息
Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
出版信息
Anal Biochem. 2014 May 15;453:4-6. doi: 10.1016/j.ab.2014.02.017. Epub 2014 Feb 26.
Abstract
Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.
摘要
血管内皮生长因子-C（VEGF-C）是一种对淋巴管生成至关重要的分泌型生长因子。VEGF-C在生理性和病理性淋巴管生成中均发挥作用，尤其是在肿瘤转移方面，这使其成为一个有吸引力的治疗靶点。两类细胞表面受体家族的成员可转导VEGF-C信号：神经纤毛蛋白-2（Nrp2）和血管内皮生长因子受体（VEGFR）-2/3。Nrp2是一个很有前景的抑制靶点，因为它在淋巴管中高度表达。在此，我们描述了一种基于微孔板的检测方法，用于发现VEGF-C/Nrp2抑制剂。我们对该检测方法进行了优化，以用于筛选抑制剂文库，并从美国国立卫生研究院（NIH）临床化合物库小分子文库中鉴定出三种新型的Nrp2/VEGF-C结合抑制剂。
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