Developing potent LC3-targeting AUTAC tools for protein degradation with selective autophagy

Autophagy-based protein degradation is emerging as a promising technology for anti-diseases and innovative drug discovery. Here, we demonstrate a novel type of autophagy-targeting chimera (AUTAC) to degrade protein by targeting autophagy key protein LC3. The best compound 10f powerfully degraded BRD4 protein through the autophagy pathway and exhibited good anti-proliferative activity in multiple tumor cells, providing a powerful toolbox for medicinal chemists to study disease-related targets with autophagy-based degradation.