Targeting RNA-binding proteins with small molecules: Perspectives, pitfalls and bifunctional molecules

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• RNA-binding proteins (RBPs) are crucial for regulating RNA functions in organisms.
• Small molecules targeting RBPs represent a promising area for therapeutic development.
• Understanding RBP-RNA interactions is key to developing novel therapeutic strategies.

Purpose of the Study:

• To provide perspectives on developing small molecule regulators of RBPs.
• To highlight key types of small molecule modulators for RBP regulation.
• To emphasize the potential of bifunctional molecules in overcoming drug discovery challenges.

Main Methods:

• Review of current strategies for small molecule RBP modulation.
• Categorization of small molecule modulators based on their mechanism of action.
• Discussion of challenges and opportunities in RBP-targeted drug discovery.

Main Results:

• Identified three main classes of small molecule modulators: direct RBP binders, bifunctional molecules, and RNA/RBP stability modifiers.
• Highlighted direct RBP binders that modulate RNA interactions.
• Emphasized bifunctional molecules for their potential to enhance RBP-RNA interaction modulation.

Conclusions:

• Small molecule regulators of RBPs hold significant therapeutic potential.
• Bifunctional molecules offer a novel approach to modulate RBP functions and overcome drug discovery hurdles.
• Further research into RBP-small molecule interactions is warranted for advancing drug development.