TAC-tics for Leveraging Proximity Biology in Drug Discovery.

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Chemically induced proximity (CIP) utilizes synthetic molecules to manipulate biological interactions.
• This field is rapidly advancing, with significant interest in basic research and drug development.

Purpose of the Study:

• To review critical advances and opportunities in chemically induced proximity.
• Focus on protein degraders, RNA degraders, and non-degrader modalities.

Main Methods:

• Review of existing literature on PROteolysis TArgeting Chimeras (PROTACs).
• Exploration of emerging induced proximity modalities beyond degradation.
• Analysis of post-translational modification (PTM) and protein-protein interaction (PPI) modulators.

Main Results:

• PROTACs are a key CIP modality, degrading target proteins via the ubiquitin-proteasome system.
• New CIP modalities are emerging to modulate both proteins and RNA.
• Non-degrader CIP approaches include PTM and PPI modulation.

Conclusions:

• Emerging proximity-based drug modalities offer new therapeutic avenues.
• These modalities are valuable tools for biological research and drug discovery.
• The field of CIP is poised for continued innovation and application.