Ligands for E3 Ligase

E3 ligases are key enzymes in the ubiquitin-proteasome system (UPS) and play a decisive role in the selective degradation of targeted proteins. The UPS system is the main protein degradation mechanism in cells. Its core function is to connect ubiquitin molecules to target proteins and mark them for proteasome degradation through the coordinated action of E1 activating enzymes, E2 ligases, and E3 ligases. E3 ligases are responsible for recognizing specific substrate proteins and transferring ubiquitin to lysine residues of proteins. This specificity makes E3 ligases occupy an important position in the field of targeted protein degradation. In the human genome, more than 600 E3 ligases have been identified, which regulate a variety of cellular processes by specifically recognizing different substrates. However, despite the wide variety of E3 ligases, most of the current research on PROTAC technology focuses on a few ligases, especially cereblon (CRBN), von Hippel–Lindau (VHL), and inhibitor of apoptosis protein (IAP). These E3 ligases have strong small molecule binding capabilities and their ligand synthesis is relatively mature, making them the main targets of current PROTAC design.