PROTAC PD-1/PD-L1 degrader-1, a PD-1/PD-L1 PROTAC based on Cereblon E3 ligand, inhibits PD-1/PD-L1 interaction with an IC50 of 39.2 nM. PROTAC PD-1/PD-L1 degrader-1 significantly restores the immunity repressed in a co-culture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. PROTAC PD-1/PD-L1 degrader-1 moderately reduces the protein levels of PD-L1 in a lysosome-dependent manner.In Vitro: PROTAC PD-1/PD-L1 degrader-1 (compound p22) reduces cell surface PD-L1 expression for more than 14%.
PROTAC PD-1/PD-L1 degrader-1 (1-10 μM; 24 hours) reduces PD-L1 expression in a dose-dependent manner by 21% and 35% at 1 μM and 10 μM, respectively.