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Cited by 231Protein Degradation and InhibitorsChemical Synthesis and AnalysisUbiquitin and proteasome pathways

Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic

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Hu, Zhenyi, Crews, Craig M.·2022·ChemBioChem
DOI 10.1002/cbic.202100270PMC PMC9395155
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Abstract

Proteolysis‐targeting chimeras (PROTACs), an emerging paradigm‐shifting technology, hijacks the ubiquitin‐proteasome system for targeted protein degradation. PROTACs induce ternary complexes between an E3 ligase and POI, and this induced proximity leads to polyUb chain formation on substrates and eventual proteasomal‐mediated POI degradation. PROTACs have shown great therapeutic potential by degrading many disease‐causing proteins, such as the androgen receptor and BRD4. The PROTAC technology has advanced significantly in the last two decades, with the repertoire of PROTAC targets increased tremendously. Herein, we describe recent developments of PROTAC technology, focusing on mechanistic and kinetic studies, pharmacokinetic study, spatiotemporal control of PROTACs, covalent PROTACs, resistance to PROTACs, and new E3 ligands.

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Cited by

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Related

Authors
Hu, Z., & Crews, C. M.
Affiliations
Yale University (US)
Corresponding author
Crews, Craig M.
ORCID
Venue
ChemBioChem
Publisher
Wiley
Published
2021-09-23
Volume
23
Issue
2
Pages
e202100270-e202100270
ISSN
  • 1439-4227 (ISSN-L)
  • 1439-7633
DOI
10.1002/cbic.202100270
PMC
PMC9395155
OpenAlex
W3198775252
Cited by
231
References
145
Citations by year
2026: 35 · 2025: 45 · 2024: 51 · 2023: 43 · 2022: 53 · 2021: 4
FWCI
4.04
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • ChemBioChem (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
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, targeted protein degradation, ubiquitin-proteasome system, E3 ubiquitin ligase, androgen receptor, BRD4, pharmacokinetics, spatiotemporal control, degradation kinetics
MeSH terms
HeLa Cells, Humans, Kinetics, Ligands, Light, Protein Conformation, Proteins, Transcription Factors, Immunoconjugates, Proteolysis

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