Recent advances and mechanisms of action of PD-L1 degraders as potential therapeutic agents

Feng Zhang, Ruiya Jiang, Shishi Sun, Caiyun Wu, Qimeng Yu,Annoor Awadasseid, Jianwei Wang,Wen Zhang

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY(2024)

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摘要
PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new opportunities for immunotherapy. Here, we mainly summarize and review the current active molecules and mechanisms that mediate the degradation of immature and mature PD-L1 during the post-translational modification stages, involving PD-L1 phosphorylation, glycosylation, palmitoylation, ubiquitination, and the autophagy-lysosomal process. This review expects that by degrading PD-L1 protein, we will not only gain a better understanding of oncogenic mechanisms involving tumor PD-L1 protein but also provide a new way to improve immunotherapy.
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关键词
PD-L1,Degradation,Post-translational modification,Tumor,Immunotherapy
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