Department of Structural and Molecular Biology, Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
Drug Discov Today. 2013 May;18(9-10):447-55. doi: 10.1016/j.drudis.2012.11.013. Epub 2012 Dec 8.
The blockade of tumour vascularisation and angiogenesis continues to be a focus for drug development in oncology and other pathologies. Historically, targeting vascular endothelial growth factor (VEGF) activity and its association with VEGF receptors (VEGFRs) has represented the most promising line of attack. More recently, the recognition that VEGFR co-receptors, neuropilin-1 and -2 (NRP1 and NRP2), are also engaged by specific VEGF isoforms in tandem with the VEGFRs has expanded the landscape for the development of modulators of VEGF-dependent signalling. Here, we review the recent structural characterisation of VEGF interactions with NRP subdomains and the impact this has had on drug development activity in this area.
阻断肿瘤血管生成和血管生成一直是肿瘤学和其他病理学药物开发的重点。从历史上看，靶向血管内皮生长因子 (VEGF) 活性及其与血管内皮生长因子受体 (VEGFR) 的关联一直是最有前途的攻击途径。最近，人们认识到，VEGFR 共受体神经纤毛蛋白 1 和 -2 (NRP1 和 NRP2) 也与 VEGFR 一起被特定的 VEGF 同工型结合，这扩展了开发 VEGF 依赖性信号转导调节剂的领域。在这里，我们回顾了 VEGF 与 NRP 亚结构域相互作用的最新结构特征，以及这对该领域药物开发活动的影响。
