Oncogenic protein interfaces: small molecules, big challenges.

Area of Science:

• Medicinal Chemistry and Drug Discovery
• Molecular Biology and Biochemistry

Background:

• Protein-protein interactions (PPIs) were historically considered 'undruggable' targets for small molecules due to their typically flat and featureless interfaces.
• Larger molecules like peptides and antibodies were the primary therapeutic agents for modulating PPIs.

Purpose of the Study:

• To review recent breakthroughs in targeting PPIs with small molecules.
• To describe novel techniques for discovering PPI modulators.
• To explain how drug discovery strategies have adapted to address these challenging targets.

Main Methods:

• Review of emerging and refined techniques for identifying small molecule modulators of PPIs.
• Analysis of adapted drug discovery pipelines for targeting PPI interfaces.

Main Results:

• Significant progress has been made in developing small molecules that can modulate PPIs.
• New techniques and a deeper understanding of PPI surfaces have enabled successful targeting.
• Current drug discovery approaches are increasingly effective against previously intractable PPI targets.

Conclusions:

• Targeting protein-protein interactions with small molecules is now a viable and advancing area of drug discovery.
• Continued innovation in techniques and strategic adaptation of discovery methods are key to future success.