Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Therapeutic resistance and the undruggable proteome limit current inhibitor-based treatments.
• Proteolysis targeting chimera (PROTAC) technology offers a novel solution by degrading target proteins.

Purpose of the Study:

• To highlight the advantages of PROTAC technology.
• To summarize the mechanisms and applications of PROTACs in biotherapeutics.
• To discuss the potential of PROTACs in clinical drug development, including antivirals.

Main Methods:

• Review of existing literature on PROTAC technology.
• Analysis of PROTAC mechanisms, focusing on the ubiquitin-proteasome system (UPS).
• Examination of therapeutic benefits and applications compared to small-molecule inhibitors.

Main Results:

• PROTACs utilize a heterobifunctional molecule to link E3 ligase and protein of interest (POI) ligands.
• Targeted protein degradation via UPS offers a new strategy for inhibiting previously undruggable proteins.
• PROTACs demonstrate therapeutic benefits over classical inhibitors in specific applications.

Conclusions:

• PROTAC technology presents a promising framework for overcoming therapeutic resistance.
• This technology opens new avenues for developing targeted protein degraders.
• PROTACs hold significant potential for clinical applications, including antiviral therapies.