Di-bromo-Based Small-Molecule Inhibitors of the PD-1/PD-L1 Immune Checkpoint.

ABSTRACT: Immune checkpoint blockade is one of the most promising strategies of cancer immunotherapy. However, unlike classical targeted therapies, it is currently solely based on expensive monoclonal antibodies, which often inflict immune-related adverse events. Herein, we propose a novel small-molecule inhibitor targeted at the most clinically relevant immune checkpoint, PD-1/PD-L1. The compound is capable of disrupting the PD-1/PD-L1 complex by antagonizing PD-L1 and, therefore, restores activation of T cells similarly to the antibodies, while being cheap in production and possibly nonimmunogenic. The final compound is significantly smaller than others reported in the literature while being nontoxic to cells even at high concentrations. The scaffold was designed using a structure-activity relatio

SUBMITTER: Konieczny M 

PROVIDER: S-EPMC7584369 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature