标题：PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules
作者：Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing
作者机构：[Geng, Qiaohong; Jiao, Peifu; Jin, Peng] Qilu Normal Univ, Dept Chem, Jinan 250013, Shandong, Peoples R China.; [Yan, Bing] Shandong Univ, Sch Envir 更多
通讯作者：Jiao, PF;Yan, B
通讯作者地址：[Jiao, PF]Qilu Normal Univ, Dept Chem, Jinan 250013, Shandong, Peoples R China;[Yan, B]Shandong Univ, Sch Environm Sci & Engn, Jinan 250100, Shandong, 更多
来源：CURRENT PHARMACEUTICAL DESIGN
关键词：Cancer immunotherapy; therapeutic antibody; small molecules; peptides;; structure-activity relationships; tumor cells
摘要：Background: The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer.; Methods: The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structure-activity relationships of peptides and small molecules as inhibitors.; Results: Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors.; Conclusion: Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors.