Design, Synthesis, and Evaluation of 8-(<i>o</i>-Tolyl)quinazoline Derivatives as Small-Molecule PD-1/PD-L1 Antagonists.

ABSTRACT: Small-molecule inhibitors targeting programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions can compensate for the shortcomings of antibody-based inhibitors and have attracted considerable attention, some of which have already entered clinical trials. Herein, based on our previous study on small-molecule PD-L1 inhibitors, we reported a series of 8-(o-tolyl)quinazoline derivatives by the skeleton merging strategy. Homogenous time-resolved fluorescence (HTRF) assay against PD-1/PD-L1 interaction identified compound A5, which showed the most potent inhibition with an IC₅₀ value of 23.78 nM. Meanwhile, based on the results of HTRF assay, the structure-activity relationships (SARs) of the tail were focused on. Cell-based PD-1/PD-L1 blockade assa

SUBMITTER: Wu X 

PROVIDER: S-EPMC11017391 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature