Perspectives of autophagy-tethering compounds (ATTECs) in drug discovery
Yu Ding,
Dong Xing,
Yiyan Fei,
Shouqing Luo,
Boxun Lu
Affiliations
Yu Ding
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Life Sciences, Fudan University, Shanghai 200438, China; Corresponding authors.
Dong Xing
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; Corresponding authors.
Yiyan Fei
Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China; Corresponding authors.
Shouqing Luo
Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Plymouth PL6 8BU, UK
Boxun Lu
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Life Sciences, Fudan University, Shanghai 200438, China; Corresponding authors.
Degrader technologies provide unprecedented strategies to tackle diseases caused by pathogenic proteins that are difficult to target by the traditional inhibitor approach. One pioneering technology, proteolysis-targeting chimera (PROTAC), has revolutionized small-molecule drug discovery. However, PROTACs hijack the ubiquitination-proteasome pathway, which is incapable of degrading certain categories of targets. To address this limitation, scientists introduced autophagy-tethering compounds (ATTECs), capitalizing on the autophagosome protein LC3 to selectively break down both pathogenic proteins and organelles. This review explores multiple dimensions of ATTECs, focusing on their mechanisms of action and potential applications in drug discovery.
