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

Eur J Med Chem. 2024 Feb 23;268:116267. doi: 10.1016/j.ejmech.2024.116267. Online ahead of print.ABSTRACTPD-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.PMID:38422701 | DOI:10.1016/j.ejmech.2024.116267
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research