Molecular Glue Discovery: Current and Future Approaches.

Area of Science:

• Biochemistry
• Pharmacology
• Drug Discovery

Background:

• Biomolecular interactions can be manipulated using small molecules, termed molecular glues, to alter cellular functions like signaling and cell cycle.
• Molecular glues that mediate novel or known protein-protein interactions present a promising therapeutic avenue.
• Developing effective molecular glues is crucial for advancing targeted therapies.

Purpose of the Study:

• To review and classify existing FDA-approved molecular glues.
• To survey and highlight key factors in small-molecule molecular glue discovery methodologies.
• To provide a guide for researchers seeking to discover novel molecular glues for therapeutic applications.

Main Methods:

• Classification of current FDA-approved molecular glues.
• Survey of two broad strategies for molecular glue discovery.
• Emphasis on critical factors including experimental conditions, software, and genetic tools.

Main Results:

• Categorization of molecular glues aids in selecting appropriate discovery approaches.
• Identification of crucial experimental and computational elements for successful molecular glue discovery.
• A framework for understanding and applying various discovery methodologies.

Conclusions:

• Molecular glues are a powerful tool for modulating cellular processes and offer therapeutic benefits.
• Systematic review of discovery methods facilitates the identification of new molecular glues.
• This work aims to inspire further research into molecular glues for diverse human diseases.