MS1-96

MS1-96 is an orally active PD-L1 (programmed death-ligand 1) degrader. It effectively reduces PD-L1 protein expression levels in various colorectal cancer (CRC) cell lines. The compound loses its ability to induce PD-L1 degradation upon HIP1R knockdown. MS1-96 binds directly to PD-L1 (KD= 2.58 μM) and enhances the interaction between HIP1R and PD-L1, altering PD-L1's intracellular transport in clathrin-coated vesicles. Additionally, MS1-96 induces abnormal N-glycosylation of PD-L1, leading to protein instability and accelerated lysosome-mediated degradation. MS1-96 is applicable for colorectal cancer research.