Cited by 46Protein Degradation and InhibitorsAutophagy in Disease and TherapyUbiquitin and proteasome pathways

Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research

Li, Xiang, Liu, Qian, Xie, Xin, Peng, Cheng, Pang, Qiwen, Liu, Bo, Han, Bo·2023·Journal of Medicinal Chemistry

Abstract

Targeted protein degradation (TPD) technology is based on a unique pharmacological mechanism that has profoundly revolutionized medicinal research by overcoming limitations associated with traditional small-molecule drugs. Autophagy, a mechanism for intracellular waste disposal and recovery, is an important biological process in medicinal research. Recently, studies have demonstrated that several emerging autophagic degraders can treat human diseases. Herein we summarize the progress in medicinal research on autophagic degraders, including autophagosome-tethering compounds (ATTEC), autophagy-targeting chimeras (AUTAC), and AUTOphagy-TArgeting chimeras (AUTOTAC), for treating human diseases. These autophagic degraders exhibit excellent potential for treating neurodegenerative diseases. Our research on autophagic degraders provides a new avenue for medicinal research on TPD via autophagy.

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Crossref · 10.1021/acs.jmedchem.2c01712

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135 of 135 references verified0 citation errors · 0 not checkable

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  • The proteasome system primarily degrades short-lived, soluble, and misfolded monomeric proteins, while the lysosomal system focuses on long-lived proteins, protein aggregates, and damaged organelles; both systems can achieve substrate degradation through ubiquitination and can collaborate to degrade the same intracellular substrate.

    “The proteasome system primarily degrades short-lived, soluble, and misfolded monomeric proteins, while the lysosomal system focuses on long-lived proteins, protein aggregates, and damaged organelles. Both systems can achieve substrate degradation through ubiquitination and can also collaborate to degrade the same intracellular substrate.”

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Authors
Li, X., Liu, Q., Xie, X., Peng, C., Pang, Q., Liu, B., & Han, B.
Affiliations
  • Chengdu University of Traditional Chinese Medicine (CN)
  • Sichuan University (CN)
Corresponding author
  • Peng, Cheng
  • Liu, Bo
  • Han, Bo
Venue
Journal of Medicinal Chemistry
Published
2023-01-30
Volume
66
Issue
3
Pages
1700-1711
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W4318539707
Cited by
46
References
135
Citations by year
2026: 14 · 2025: 13 · 2024: 10 · 2023: 9
FWCI
1.21
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chengdu University of Traditional Chinese Medicine
  • Department of Science and Technology of Sichuan Province (2022JDRC0045, 2022NSFSC0626)
  • National Health Commission of the People's Republic of China (ZYYCXTD-D-202209)
  • National Natural Science Foundation of China (82073998, 82104376)
  • Sichuan Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
targeted protein degradation, autophagy, neurodegenerative diseases, drug development
MeSH terms
Autophagosomes, Autophagy, Humans, Neurodegenerative Diseases, Proteolysis

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