Lamminmaki Urpo, Nikolov Dimitar, Himanen Juha
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Curr Drug Targets. 2015;16(10):1021-30. doi: 10.2174/1389450116666150531154619.
The Eph receptors are the largest sub-family of Receptor Tyrosine Kinases (RTK). They, together with their ephrin ligands, play central roles in cell-cell communication during development, and also in the maintenance of a normal adult physiology. Their malfunction, therefore, can contribute to various human diseases. Since the structures of the Eph receptors and ephrins are by now well characterized, there has been extensive recent work to develop ways to manipulate their action in order to achieve therapeutic benefits. Although few reagents have progressed to clinical trials thus far, it is evident that the Eph receptors are valid targets for therapeutic drugs. In this review we first summarize studies on the three-dimensional structures of Eph receptors. We then give an overview on small molecule inhibitors and activators using Ephs as targets. We put a special focus on the latest developments in the field of monoclonal antibodies and antibody fragments for inhibiting or activating the Eph/ephrin signaling.
Eph受体是受体酪氨酸激酶（RTK）中最大的亚家族。它们与其 ephrin 配体一起，在发育过程中的细胞间通讯以及维持正常成人生理功能方面发挥着核心作用。因此，它们的功能失调会导致各种人类疾病。由于目前 Eph 受体和 ephrin 的结构已得到充分表征，最近有大量工作致力于开发操纵它们作用的方法以实现治疗益处。尽管到目前为止很少有试剂进入临床试验，但很明显 Eph 受体是治疗药物的有效靶点。在这篇综述中，我们首先总结关于 Eph 受体三维结构的研究。然后概述以 Ephs 为靶点的小分子抑制剂和激活剂。我们特别关注用于抑制或激活 Eph/ephrin 信号传导的单克隆抗体和抗体片段领域的最新进展。
