Targeted protein degradation: species, diseases and efficient utilization.

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Targeted protein degradation (TPD) represents a novel therapeutic strategy distinct from traditional inhibitors.
• TPD utilizes endogenous clearance pathways like the ubiquitin-proteasome system (UPS) and lysosomal pathway to eliminate target proteins.
• Current TPD formulations face challenges including poor bioavailability and off-target effects, limiting clinical translation.

Purpose of the Study:

• To provide a comprehensive overview of existing TPD strategies and their mechanisms.
• To summarize the research progress of TPD in key disease areas such as oncology, neurodegenerative disorders, and inflammatory/immune diseases.
• To discuss the role of drug delivery systems in overcoming TPD limitations and enhancing therapeutic outcomes.

Main Methods:

• Review of different TPD strategies and their implementation mechanisms.
• Summary of current research on TPD applications in major disease fields.
• Discussion on the potential of drug delivery systems for TPD formulation enhancement.

Main Results:

• TPD strategies include various approaches for protein labeling and degradation.
• TPD shows promise in tumor therapy by targeting key proteins like Bruton Tyrosine Kinase (BTK), Androgen Receptor (AR), and Estrogen Receptor (ER).
• Drug delivery systems hold significant potential to improve TPD bioavailability and specificity.

Conclusions:

• This review offers a detailed understanding of TPD types, disease applications, and optimization strategies.
• Effective application of TPD requires addressing formulation challenges.
• The findings are expected to guide the development of novel TPD formulations and accelerate clinical translation.