The traditional drug discovery and development mainly focuses on directly regulating the activity of proteins or enzymes to treat diseases, mainly through the pharmacological mode of occupancy-driven to control the function of proteins. It is estimated that only 10% of proteins can be regulated by small molecules, and 10% of proteins that can be regulated by biological macromolecules are on the cell surface. And up to 80% of the proteins can't be regulated by existing drugs. Therefore, PROTAC is emerging as a promising technique in the development of therapeutics. In the process of its development, scientists found that the ability of PROTAC to induce degradation is not only related to target binding, the identity of inhibitor warheads and recruited E3 ligases largely determine the degradation of compounds. Therefore, for PROTAC development, the identification of specific ligands is very important to determine the specificity of PROTAC molecules, both the target ligand and the recruited E3 ligase should be changed to quickly produce PROTAC with the desired degradation characteristics.
