Date of Original Version
Biomedical and Pharmaceutical Sciences
Programmed death-1/programmed death ligand-1 (PD-1/PD-L1) based immunotherapy is a revolutionary cancer therapy with great clinical success. The majority of clinically used PD-1/PD-L1 inhibitors are monoclonal antibodies but their applications are limited due to their poor oral bioavailability and immune-related adverse effects (irAEs). In contrast, several small molecule inhibitors against PD-1/PD-L1 immune checkpoints show promising blockage effects on PD-1/PD-L1 interactions without irAEs. However, proper analytical methods and bioassays are required to effectively screen small molecule derived PD-1/PD-L1 inhibitors. Herein, we summarize the biophysical and biochemical assays currently employed for the measurements of binding capacities, molecular interactions, and blocking effects of small molecule inhibitors on PD-1/PD-L1. In addition, the discovery of natural products based PD-1/PD-L1 antagonists utilizing these screening assays are reviewed. Potential pitfalls for obtaining false leading compounds as PD-1/PD-L1 inhibitors by using certain binding bioassays are also discussed in this review.
Publication Title, e.g., Journal
Cancer Cell International
Liu, C., Seeram, N.P. & Ma, H. Small molecule inhibitors against PD-1/PD-L1 immune checkpoints and current methodologies for their development: a review. Cancer Cell Int 21, 239 (2021). https://doi.org/10.1186/s12935-021-01946-4
Available at: https://doi.org/10.1186/s12935-021-01946-4
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