Protein-protein interactions as drug targets

Area of Science:

• Drug discovery and chemical biology
• Medicinal chemistry
• Structural biology

Background:

• Protein-protein interactions (PPIs) were once considered undruggable targets.
• Recent advancements demonstrate the feasibility of modulating PPIs with small molecules.
• Targeting PPIs is crucial for developing novel therapeutics.

Purpose of the Study:

• To summarize the current state of small-molecule inhibition and stabilization of PPIs.
• To review active molecules from a structural and medicinal chemistry perspective.
• To highlight key examples of successful PPI modulation.

Main Methods:

• Literature review of small-molecule modulators of PPIs.
• Analysis of active molecules based on structural and medicinal chemistry principles.
• Focus on specific PPI targets including iNOS, LFA-1, and 14-3-3.

Main Results:

• Small-molecule inhibition and stabilization of PPIs is an emerging and successful strategy.
• Numerous active molecules targeting PPIs have been identified and characterized.
• Key examples demonstrate the potential of targeting iNOS, LFA-1, and 14-3-3.

Conclusions:

• Modulating PPIs with small molecules is a viable and important approach in drug discovery.
• Structural and medicinal chemistry insights are key to developing effective PPI-targeting drugs.
• Continued research in this area promises significant therapeutic advancements.