靶向PD-1/PD-L1蛋白-蛋白相互作用小分子抑制剂研究进展  

Research Progress of Small Molecule Inhibitors Targeting PD-1/PD-L1 Protein-protein Interaction

作　　者：宋伟 段学民 程建昕 SONG Wei;DUAN Xuemin;CHENG Jianxin(Jiangxi Provincial Key Laboratory of Drug Design and Evaluation,School of Pharmacy,Jiangxi Normal University of Science and Technology,330013,Nanchang,PRC)

机构地区：[1]江西科技师范大学药学院,江西省药物分子设计与评价重点实验室,南昌330013

出　　处：《江西科学》2024年第3期482-489,共8页Jiangxi Science

基　　金：国家自然科学基金项目(22063004)。

摘　　要：目的:阐述PD-1/PD-L1的相互作用机制及其在癌细胞免疫逃逸上的作用,并介绍近几年开发的靶向PD-1/PD-L1的新型小分子抑制剂。方法:检索国内外PD-1/PD-L1抑制剂的文献,整理和比较近几年开发的靶向PD-1/PD-L1的小分子抑制剂。结果:PD-1/PD-L1抑制剂主要包括单克降抗体、拟肽抑制剂和小分子抑制剂,主要通过阻断PD-1/PD-L相互作用,形成PD-L1二聚体发挥作用。意义:开发靶向PD-1/PD-L1的小分子药物是一个具有挑战性的过程,小分子抑制剂具有比抗体更好的抑制肿瘤生长和迁移的能力,近几年小分子抑制剂的设计思路为小分子抑制剂的设计提供了新的思路。Objective:To elucidate the interaction mechanism of PD-1/PD-L1 and its role in immune escape of cancer cells,and to introduce novel small molecule inhibitors targeting PD-1/PDL1 developed in recent years.Methods:Literature on PD-1/PD-L1 inhibitors from domestic and foreign sources was searched,and the small molecule inhibitors targeting PD-1/PD-L1 developed in recent years were collated and compared.Results:PD-1/PD-L1 inhibitors mainly include monoclonal antibodies,peptidomimetic inhibitors,and small molecule inhibitors,which mainly exert their effects by blocking the interaction between PD-1 and PD-L1,forming PD-L1 dimers.Significance:The development of small molecule drugs targeting PD-1/PD-L1 is a challenging process.Small molecule inhibitors have better abilities to inhibit tumor growth and migration compared to antibodies.The design strategies of small molecule inhibitors in recent years have provided new insights for the development of small molecule inhibitors.

关 键 词：免疫逃逸 PD-1/PD-L1 单克隆抗体 小分子抑制剂 

分 类 号：R914.2[医药卫生—药物化学]