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