PD-1/PD-L1小分子抑制剂研究进展  

Research Progress on Small Molecule Inhibitors of PD-1/PD-L1

作　　者：张大猛 陈美宇 徐静 杜沛龙 朱馨婷 韩冷 郭澄[1] 杨全军[1] ZHANG Dameng;CHEN Meiyu;XU Jing;DU Peilong;ZHU Xinting;HAN Leng;GUO Cheng;YANG Quanjun(The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China 200233;Shanghai University of Medicine&Health Sciences,Shanghai,China 201318)

机构地区：[1]上海交通大学医学院附属第六人民医院,上海200233 [2]上海健康医学院,上海201318

出　　处：《中国药业》2024年第12期1-6,共6页China Pharmaceuticals

基　　金：国家自然科学基金[82272925];上海市浦江人才计划项目[21PJ1411900];上海市第六人民医院院级管理类科研基金[沪六院内科字〔2023〕第1号];上海市第六人民医院医疗服务能级提升工程医政管理优化项目[20220201]。

摘　　要：目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总并分析该类制剂的研发现状。结果与结论有成药潜力的PD-1/PD-L1小分子抑制剂共20种,包括CA-170(口服小分子抑制剂)、INCB086550(特异性PD-L1抑制剂)、DPPA-1(特异性抑制PD-1/PD-L1相互作用的多肽类拮抗剂)等,其中前两者已进入临床试验阶段。PD-1/PD-L1小分子抑制剂具有特异性抑制免疫检查点的药效作用特点,以及可口服、稳定性较好、膜通透性较高等优点,但其治疗效果仍需临床试验验证。Objective To provide a reference for the research and development(R&D)of novel small molecule inhibitors of programmed death-1(PD-1)/programmed death-ligand 1(PD-L1).Methods The studies related to small molecule inhibitors of PD-1/PD-L1 in the PubMed,Embase,Web of Science,ClinicalTrails.gov,CNKI and WanFang databases from 2010 to 2023 were searched to summarize and analyze the R&D status of these inhibitors.Results and Conclusion There are 20 small molecule inhibitors of PD-1/PD-L1 with the potential to develop into drugs,including CA-170(oral small molecule inhibitor),INCB086550(specific PD-L1 inhibitor),DPPA-1(peptide antagonists specifically inhibiting the interaction of PD-1/PD-L1)and so on.The first two are already in clinical trial stage.The small molecule inhibitors of PD-1/PD-L1 can specifically inhibit immune checkpoints,and they can be taken orally,have good stability and high membrane permeability,but their therapeutic effects still need to be verified through clinical trials.

关 键 词：程序性死亡受体-1 程序性死亡配体-1 小分子抑制剂 免疫检查点 抗肿瘤药物 靶向治疗 

分 类 号：R979.19[医药卫生—药品]