Induced-Proximity Therapeutics for Targeted Protein and RNA Degradation: An Organic Chemistry Perspective π§¬⚗️
Induced-proximity therapeutics are transforming modern drug discovery by enabling the selective degradation of disease-causing proteins and RNA instead of merely inhibiting them. π This strategy uses small organic molecules to bring a target biomolecule close to cellular degradation machinery, triggering its removal. From an organic chemistry viewpoint, the careful design of bifunctional ligands, linkers, and reactive warheads is essential for controlling stability, selectivity, and biological performance. These concepts are best seen in emerging platforms like PROTACs and RIBOTACs. π¬✨ Organic chemistry plays a central role in optimizing these systems by tuning functional groups, stereochemistry, and molecular interactions . π§ͺ By engineering precise proximity between enzymes and targets, chemists can achieve efficient and controllable degradation. This approach overcomes limitations of traditional inhibitors, especially for “undruggable” proteins. Smart linker design, pol...