Perspectives of autophagy-tethering compounds (ATTECs) in drug discovery

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, PR...

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Bibliographic Details
Published inMedicine Plus Vol. 1; no. 1; p. 100004
Main Authors Yu Ding, Dong Xing, Yiyan Fei, Shouqing Luo, Boxun Lu
Format Journal Article
LanguageEnglish
Published KeAi Communications Co., Ltd 01.03.2024
Subjects
Autophagy
Degrader
Drug discovery
High-throughput screening
LC3
Targeted degradation
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Summary: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.
ISSN:2950-3477
DOI:10.1016/j.medp.2023.100004