PROTAC: Innovative Technology for Targeted Protein Degradation
PROTAC (Proteolysis-Targeting Chimeras) represents a revolutionary targeted protein degradation technology. It harnesses the cell’s innate ubiquitin–proteasome system to achieve highly selective degradation of specific disease-related proteins. Unlike traditional small-molecule inhibitors that merely “block” protein function, PROTACs can completely “eliminate” pathogenic proteins, thereby offering more durable therapeutic effects.
Mechanism Overview
PROTAC is a bifunctional molecule capable of simultaneously binding to both a target protein and an E3 ubiquitin ligase. This induces proximity, leading to the formation of a stable ternary complex with a specific spatial configuration. The E3 ligase then transfers a polyubiquitin chain to the target protein, marking it for degradation. The ubiquitinated target protein is subsequently recognized and thoroughly degraded by the proteasome system. Following degradation, the PROTAC molecule is released and can catalytically initiate another round of degradation, enabling efficient, event-driven efficacy. This catalytic mechanism, resembling an enzymatic reaction, allows PROTACs to function at low concentrations, thereby reducing side effects associated with high drug doses.
Technical Advantages
- Ability to target traditionally “undruggable” targets
- High selectivity and long-lasting action
- Catalytic mechanism with efficacy at low doses
