Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway

摘要

Tumor cells form immune escape and subsequently obtain unlimited proliferation ability due to the abnormal immune surveillance mediated by immune checkpoints.Among this class of immune checkpoints,PD-1/PD-L1 was recognized as an anticancer drug target for many years,and so far,several monoclonal antibodies have achieved encouraging outcome in cancer treatment by targeting the PD-1/PD-L1 signaling pathway.Due to the inherent limitations of antibodies,the development of small molecule inhibitors based on PD-1/PD-L1 signaling pathway is gradually reviving in decades.In this review,we summarized a number of small molecule inhibitors based on three different therapeutic approaches interfering PD-1/PD-L1 signaling pathway:(1)blocking direct interaction between PD-1 and PD-L1;(2)inhibiting transcription and translation of PD-L1;and(3)promoting degradation of PD-L1 protein.The development of these small molecule inhibitors opens a new avenue for tumor immunotherapy based on PD-1/PD-L1 signaling pathway.