Targeted Protein Degradation: Methods and Prospects

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Targeted proteolysis systems are emerging as powerful therapeutic tools.
• These systems enable the directed degradation of pathogenic proteins.

Purpose of the Study:

• To review key mechanisms and recent advances in inducible targeted proteolysis.
• To discuss various degradation platforms including PROTACs, LYTACs, and BacPROTACs.
• To explore the therapeutic potential and challenges of these technologies.

Main Methods:

• Systematic review of targeted proteolysis mechanisms.
• Analysis of structural features, advantages, and limitations of degradation platforms.
• Review of preclinical and clinical efficacy data.

Main Results:

• Covers targeted proteasomal degradation (PROTACs, AbTACs, molecular glues).
• Includes lysosome-mediated degradation (LYTACs, AUTACs, ATTECs) via endocytosis or autophagy.
• Discusses targeted proteolysis in bacteria (BacPROTACs) for prokaryotic systems.

Conclusions:

• Targeted proteolysis offers novel therapeutic strategies for cancer, neurodegenerative disorders, and infectious diseases.
• Key platforms demonstrate preclinical and clinical efficacy.
• Overcoming challenges in selectivity and in vivo delivery is crucial for therapeutic translation.