YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer.

ABSTRACT: PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized m

SUBMITTER: Lai F 

PROVIDER: S-EPMC9214057 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature