Development of a potent benzonitrile-based inhibitor of glutaminyl-peptide cyclotransferase-like protein(QPCTL)with antitumor efficacy  

作　　者：Lei Yu Pengcheng Zhao Yaoliang Sun Zening Zheng Wenhao Du Lishan Zhang Yaxu Li Longyan Xie Shilin Xu Ping Wang 

机构地区：[1]Tongji University Cancer Center,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,China [2]Department of Medicinal Chemistry,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第1期44-46,共3页信号转导与靶向治疗（英文）

基　　金：was supported by grants from the National Natural Science Foundation of China(2220708,82341028,82103973);Shanghai Sailing Program(22YF1433500,22YF1457500);Key R&D Projects in Ningxia Hui Autonomous Region(2021BFH03001).

摘　　要：Dear Editor,Immune checkpoint therapies manipulating the immune system to eliminate tumor cells have shown remarkable clinical efficacy in treating various cancers.CD47,an emerging efficient immune checkpoint,is crucial for cancer cells to evade macrophagemediated phagocytosis by interaction with signal-regulatory proteinα(SIRPα).Antibodies blocking the CD47/SIRPαinteraction have been effective to promote macrophage-mediated phagocytosis in various types of cancer in mice and humans.CD47 is not only highly expressed in tumor cells,but also normal cells,such as red blood cells(RBCs).Thus,during clinical trials involving cancer patients,anti-CD47 antibodies may promote the macrophagesmediated phagocytosis of RBCs,ultimately inducing undesirable anemia side effects.In contrast,small molecule inhibitors interrupting CD47/SIRPαaxis have shown potential to overcome the anemia,possibly due to their lower immunogenicity and shorter half-life compared to antibodies.1 Hence,developing the novel strategies,especially those without the anemia side effect,to intervene in CD47/SIRPαinteraction will benefit cancer immunotherapy.

关 键 词：ANEMIA OVERCOME eliminate 

分 类 号：R730.51[医药卫生—肿瘤]