趋化因子受体CCR4识别拮抗剂配体的机制研究

趋化因子受体CCR4是肿瘤免疫治疗及自身免疫性等疾病的重要靶标，小分子拮抗剂类配体已展现出疾病治疗的潜力。但由于趋化因子类受体亚型多、正位口袋保守性较高，在一定程度上阻碍了选择性药物的开发。在前期的研究背景下（共同第一作者: Cell, 2021; Nat. Commun. 2020），为了理解CCR4的结构与功能的关系，我们通过结构生物学和药理学等多种手段研究受体识别不同类型拮抗剂配体的分子机制，目前已获得初步的三维结构模型。总之，该研究将为有效药物设计提供结构基础。

Chemokine receptor CCR4 is an important therapeutic target for cancer and autoimmune diseases, small-molecule antagonists of CCR4 has been reported to have the ability to treat related diseases. However, the development of selective drug for CCR4 was hindered, due to the conserved orthosteric sites in large member chemokine receptors. In our previous research background of GPCR (Co-first author: Cell, 2021; Nat. Commun. 2020), we are struggling to understand the relationship between structure and function of CCR4, here, we are planning to study the detailed antagonist recognition by CCR4 through structural biology and pharmacology. So far, the initial structure model of CCR4 has been determined by our group. Together, our study would provide a structural basis for effective drug design.