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Updated: Aug 26, 2025
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Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
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Natural product-based PROteolysis TArgeting Chimeras (PROTACs).
Miaomiao Liu1, Alexander P Martyn2, Ronald J Quinn1
1Griffith Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia. r.quinn@griffith.edu.au.
Natural Product Reports
|October 5, 2022
Summary
Natural products offer unique protein recognition for drug development. This review explores their potential in Proteolysis Targeting Chimeras (PROTACs) for novel therapeutic strategies.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Pharmacology
Background:
- Natural products possess inherent ligand-protein recognition due to their biosynthetic origins.
- Protein degradation is an emerging therapeutic modality with clinical applications.
- Existing therapeutic strategies include direct natural product use, pharmacophore development, and antibody conjugates.
Purpose of the Study:
- To review the potential of natural products in the development of Proteolysis Targeting Chimeras (PROTACs).
- To discuss the chemical synthesis and challenges associated with natural product-based PROTACs.
- To highlight methods for detecting PROTAC-induced ternary complexes.
Main Methods:
- Literature review focusing on natural products and PROTAC technology.
- Analysis of biosynthetic pathways and enzyme-substrate interactions.
- Summary of chemical synthesis strategies and detection methods for ternary complexes.
Main Results:
- Natural products provide a valuable scaffold for designing PROTACs due to their specific protein binding.
- PROTACs offer a complementary approach to traditional drug development using natural products.
- Challenges in synthesis and the importance of ternary complex formation are discussed.
Conclusions:
- Natural product-derived PROTACs represent a promising avenue for novel therapeutics.
- Further research into synthesis and mechanism is crucial for clinical translation.
- This approach broadens the scope of natural products in drug discovery.
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