Development of Indole Alkaloid-Type Dual Immune Checkpoint Inhibitors Against CTLA-4 and PD-L1 Based on Diversity-Enhanced Extracts.

ABSTRACT: Cancer immunotherapy involves the use of the immune system for cancer treatment. Recently, immune checkpoint-blocking antibodies have become integral for the treatment of some cancers. However, small molecules exhibit advantages over monoclonal antibody drugs, such as cell penetration, long half-life, and low manufacturing costs, and the possibility of oral administration. Thus, it is imperative to develop small-molecule immune checkpoint inhibitors. Previously, we have screened a library of synthetic indole-alkaloid-type compounds, which are produced by diversity-enhanced extracts of Japanese cornelian cherry, and reported that an unnatural pentacyclic compound inhibits CTLA-4 gene expression. In this study, immune checkpoint inhibitors with increased potency were developed by introducing

SUBMITTER: Suzuki Y 

PROVIDER: S-EPMC8630621 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature