摘要
PD-1/PD-L1是维持机体稳态的免疫检查点共抑制分子,与肿瘤免疫逃逸密切相关。目前全球已有22款PD-1/PD-L1单抗获批用于治疗各类恶性肿瘤,然而小分子抑制剂的研发却进展缓慢。自2015年百时美施贵宝公司公开第一份联苯类化合物专利以来,至今已有15款PD-1/PD-L1小分子抑制剂进入临床开发。本文从简介PD-1/PD-L1的结构和信号通路出发,分析部分PD-1/PD-L1小分子抑制剂的临床前研究,侧重综述该类小分子抑制剂临床研究的进展。
PD-1/PD-L1 is an immune checkpoint co-suppressor molecule that maintains homeostasis in the body and is closely related to tumor immune escape. At present, 22 types of PD-1/PD-L1 monoclonal antibody have been approved globally for the treatment of various therioma, while the development of small molecule inhibitors is progressing slowly. Since the disclosure of the first patent for biphenyl compounds by Bristol Myers Squibb Company in 2015, 15 types of PD-1/PD-L1 small molecule inhibitor have been developed in clinical trials to date. This article starts with an introduction to the structure and signaling pathways of PD-1/PD-L1, analyzes the preclinical studies of some small molecule inhibitors of PD-1/PD-L1, and focuses on reviewing the progress of clinical research on this type of small molecule inhibitor.
作者
杨帆
刘敦恺
王悦
文博杰
赖宜生
Fan Yang;Dunkai Liu;Yue Wang;Bojie Wen;Yisheng Lai(Center of Drug Discovery,State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing Jiangsu)
出处
《药物化学》
2024年第2期77-86,共10页
Hans Journal of Medicinal Chemistry
基金
国家自然科学基金项目(22277142)。
