In Vitro Evaluation of PROTAC Molecules

PROTAC (proteolysis-targeting chimera) are bifunctional specific small molecules that can target otherwise undruggable target proteins for degradation, thereby reducing their biological activity in a cell. It can be understood as a dumbbell-shaped chimera, of which one end is used to target the target protein to be degraded, the other end is used to recruit protein degradation systems like E3 ubiquitin ligase and both ends are connected by a suitable linker. Therefore, a ternary chimera is formed featuring target protein - PROTAC - E3 ubiquitin ligase that ensures close connection between target protein and E3 ligase, so that the target protein can be ubiquitinated and then further recognized and degraded by proteasome.

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