Degradation of proteins by PROTACs and other strategies
Open accessAbstract
Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identification of the structure of the first ternary eutectic complex, extra-terminal domain-4-PROTAC-Von-Hippel-Lindau (BRD4-PROTAC-VHL), and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019. These discoveries strongly proved the value of the PROTAC strategy. In this perspective, we summarized recent meaningful research of PROTAC, including the types of degradation proteins, preliminary biological data in vitro and in vivo, and new E3 ubiquitin ligases. Importantly, the molecular design, optimization strategy and clinical application of candidate molecules are highlighted in detail. Future perspectives for development of advanced PROTAC in medical fields have also been discussed systematically.
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It has become routine to generate and characterize a new degrader in cell culture experiments and animal models of disease using either VHL or CRBN as a recruiting ligase.
“Accordingly, it has become routine to generate and characterize a new degrader in cell culture experiments and animal models of disease, using either VHL or CRBN as a recruiting ligase93.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [93]
PROTACs derived from different ligand tethering sites could have significantly different potency and selectivity profiles.
“PROTACs derived from different ligand tethering sites could have significantly different potency and selectivity profiles [74, 75, 76].”
From PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics (2020) · cites this paper as [76]
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References 285 · Cited by 335
Research works printed but not linked: 1
- [283]Arvinas presents preclinical data on protein degrader, ARV-471, at the 2018 San Antonio breast cancer symposium (SABCS) [Internet]. [updated 2018 Dec 9]. Available from: http://www.firstwordpharma.com/node/1610303?tsid=17#axzz5tROLEB8T.
- Authors
- Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Liu, Wenyuan
- Sun, Haopeng
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 10
- Issue
- 2
- Pages
- 207-238
- ISSN
- 2211-3835 (ISSN-L)
- PMC
- PMC7016280
- OpenAlex
- W2968014120
- Cited by
- 335
- References
- 285
- Citations by year
- 2026: 45 · 2025: 50 · 2024: 43 · 2023: 44 · 2022: 60 · 2021: 48 · 2020: 41 · 2018: 3 · 2017: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- PROTACs, protein degradation, targeted protein degradation, scaffold proteins, protein aggregation, E3 ubiquitin ligase, prostate cancer, clinical trials
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