Developing potent LC3-targeting AUTAC tools for protein degradation with selective autophagy
Junping Pei, Xiaoli Pan, Aoxue Wang, Shuai Wen, Faqian Bu, Pan Tang, Shuai Zhang, Yiwen Zhang, Guan Wang, Liang Ouyang
Abstract
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.
Topics & Concepts
AutophagyProtein degradationDrug discoveryBAG3Cell biologyChemistryDegradation (telecommunications)Cancer researchBiologyBiochemistryComputer scienceApoptosisTelecommunicationsProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysHistone Deacetylase Inhibitors Research