Small-Molecule-Induced Protein Polymerization: Mechanisms and Therapeutic Implications

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Small molecules inducing protein polymerization are an emerging therapeutic class.
• These compounds target diverse proteins, including PML-RARα, BCL6, STING, β-tubulin, and p62.
• Protein polymerization plays a critical role in cellular function and disease pathogenesis.

Purpose of the Study:

• To provide a comprehensive overview of five small molecules that induce protein polymerization.
• To explore their distinct molecular mechanisms, structural insights, and therapeutic potential.
• To highlight applications in targeted protein degradation, cancer therapy, and modulation of cellular processes.

Main Methods:

• Review of existing literature on arsenic trioxide (As2O3), BI-3802, NVS-STG2, paclitaxel, and verteporfin.
• Analysis of their protein targets and polymerization-inducing mechanisms.
• Examination of their therapeutic implications in various diseases.

Main Results:

• Arsenic trioxide and BI-3802 induce polymerization for protein degradation.
• NVS-STG2 activates protein function via polymerization.
• Paclitaxel stabilizes tubulin polymers, while verteporfin causes covalent cross-linking.

Conclusions:

• The diverse mechanisms of these small molecules highlight the complexity of protein polymerization in health and disease.
• These compounds offer significant potential for targeted protein degradation and novel therapeutic strategies.
• Further research into protein polymerization modulators can drive drug discovery and development.