Research into PD-L1 is critical in the development of small-molecule anti-cancer drugs. The current chemical compounds that bind to PD-1/PD-L1 exhibit lower efficacy than clinically relevant monoclonal antibodies, necessitating the need for new inhibitors. The aim of this study was to identify and characterise small-molecule inhibitors of PD-1/PD-L1 interaction. In this study, 1,900 compounds were screened against the PDL-1 target to identify binders using the ICM program. Virtual characterization by SwissADME of chemical scaffolds exhibiting high binding affinity to PD-L1 was performed. This was followed by the evaluation of the compounds for their PD-L1/PD-1 inhibitory activity in an in vitro ELISA assay, compared to the control. Analysis of the inhibition of the PD-L1 and PD-1 interaction revealed significant inhibition of the interaction with four compounds (Compound 3; X86577), (Compound 4; X02079), (Compound 6; X53550), and (Compound 9; X14474) compared to the anti-PD-1 neutralizing antibody. The findings present optimised small-molecule inhibitors targeting the PD-1/PD-L1 pathway, which could serve as effective immune checkpoint inhibitors. This work provides valuable insight into therapeutic solutions in addressing unmet medical needs in the oncology field.
Damfo et al. (Thu,) studied this question.