Biarylacetamides: a novel class of late-stage autophagy inhibitors.

ABSTRACT: Targeting autophagy is believed to hold great promise for the treatment of various diseases, including cancer. However, since the therapeutic efficacy of currently available autophagy-modulating drugs is limited by off-target effects and the requirement of high dosage, there is an urgent need to develop novel autophagy-targeting compounds. In this study, we report molecules of the biarylacetamide class as novel autophagy inhibitors. These molecules were identified via phenotypic high-throughput screening, and a series of analogues was subsequently synthesized. Among these, 5d and 5j were retained as potent autophagy blockers in HeLa and LNCaP cells. Both compounds inhibited autophagy at a late-stage in the pathway, as evidenced by the strong accumulation of RFP-GFP-LC3 puncta

SUBMITTER: Lallier M 

PROVIDER: S-EPMC12439681 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature