Small molecule compounds focus on inhibiting the function of disease-related proteins. However, a new concept that rather eliminates the disease-related proteins has emerged. It is a rising strategy that not only eliminates previously undruggable disease targets, but also overcomes resistance caused by pre-existing drugs.
Intracellular protein degradation takes place via two pathways led by lysosome and proteasome. Most intracellular proteins are tagged by ubiquitin and are degraded by proteasome in the cytoplasm and the nucleus. This purification process is called the Ubiquitin-Proteasome System (UPS).
PROTAC is a technology that utilizes the UPS system, an intracellular purification system. PROTAC is a bifunctional molecule where “ligand”, which binds to target protein, and “binder”, which binds to E3 ubiquitin ligase, are connected by a linker. In other words, PROTAC is a powerful inhibitor technology that enables target protein degradation and consequent therapeutic effects by placing a disease-related target protein nearby E3 ligase, which is an enzyme that can initiate the protein degradation system.