Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research
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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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.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [536]
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
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Self-citation
- 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
- Publisher
- American Chemical Society (ACS)
- 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
- Licence
- 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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