In Vitro Evaluation of PROTAC Molecules

PROTACs (proteolysis-targeting chimeras) are bifunctional small molecules that can target otherwise undruggable proteins for degradation, thereby reducing their biological activity in a cell. They can be understood as dumbbell-shaped chimeras, with one end targeting the protein to be degraded and the other recruiting protein degradation systems such as E3 ubiquitin ligase, connected by a suitable linker. This forms a ternary chimera featuring the target protein, PROTAC, and E3 ubiquitin ligase, ensuring close proximity between the target protein and E3 ligase. Consequently, the target protein can be ubiquitinated, recognized, and further degraded by the proteasome.

In theory, this new mechanism can target all drug target proteins, especially those previously considered undruggable, thereby expanding the field of drug research and promising prospects for new drug R&D. PROTAC technology is novel and offers many advantages compared to traditional micromolecule drugs, antibody drugs, and RNAi. It is considered one of the most popular new modalities in drug discovery, and Medicilon has extensive experience in PROTAC development.