Synthetic small-molecule RNA ligands: future prospects as therapeutic agents

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Molecular Biology

Background:

• Biologically relevant RNAs are crucial drug targets for various pathologies.
• Prokaryotic ribosomal RNA, viral RNAs, and oncogenic microRNAs are key examples.
• Oligonucleotides are effective RNA-targeting agents but have limitations in pharmacodynamics and pharmacokinetics.

Purpose of the Study:

• To review synthetic small-molecule ligands targeting RNA.
• To highlight compounds with selectivity suitable for clinical studies.
• To discuss strategies for enhancing RNA-targeting compound selectivity and activity.

Main Methods:

• Screening of chemical libraries for RNA binders.
• Focused design of synthetic small-molecule RNA ligands.
• Review of existing literature on selective RNA-targeting compounds.

Main Results:

• Identification of numerous synthetic small-molecule RNA ligands.
• Several compounds demonstrate sufficient selectivity for potential clinical development.
• Strategies for improving selectivity and biological activity are being explored.

Conclusions:

• Synthetic small molecules offer a promising alternative to oligonucleotides for RNA-targeted drug discovery.
• Further research into compound design and optimization is crucial for therapeutic applications.
• Targeting RNA with small molecules holds significant potential for treating cancer, infections, and other diseases.