Wise E, Pease J E
Leukocyte Biology Section, NHLI Division, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Biochem Soc Trans. 2007 Aug;35(Pt 4):755-9. doi: 10.1042/BST0350755.
Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine-chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated.
趋化因子是一类小的碱性蛋白家族，它们通过与特定的G蛋白偶联受体（GPCRs）结合，诱导细胞（尤其是白细胞）的定向迁移。趋化因子及其受体与许多临床上重要的疾病有关，这使得人们认为拮抗趋化因子-趋化因子受体网络可能具有治疗优势。因此，人们在开发趋化因子受体的小分子拮抗剂方面投入了大量精力，文献中也描述了几种这样的化合物。这种研究活动的一个奇特副产品是发现了几种受体的小分子激动剂，它们通常是在对先导拮抗剂进行优化后发现的。在这篇综述中，我们讨论了这些发现，并得出结论，这些小分子激动剂可能有助于进一步了解趋化因子受体被激活的分子机制。
