Research progress in targeted PD-L1 related inhibitors and degraders
Tumor immunotherapy is revolutionizing the treatment approach for cancer,and has significantly improved overall survival and progression-free survival in various types of cancer patients.The mechanism of action for immune checkpoint inhibitors involves blocking the interaction between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1),thereby reactivating the anti-cancer activity of cytotoxic T cells and exerting an immune-mediated anti-cancer effect.However,the PD-1/PD-L1 monoclonal antibody has a clinical efficacy rate of only about 10％-30％,and can also cause severe treatment-related adverse reactions such as immune myocarditis.Small molecule compounds have several advantages in terms of pharmacokinetics,such as better oral bioavailability,higher penetration into relevant tissues and tumor cells,and reasonable half-life.Currently,the development of small-molecule tumor immunotherapeutic drugs has become a highly active research field in cancer immunotherapy.This article aims to summarize the recent advancements in small molecule research for tumor immunotherapy over the past five years,including PD-L1 small molecule inhibitors,PD-L1 degraders based on proteolysis-targeting chimeras,and lysosome-targeting chimeras technologies,and discuss the future directions for the development of small molecule inhibitors,providing new theoretical references for tumor immunotherapy.
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