Thalidomide-NH-PEG1-C2-NH2 is a Thalidomide -based cereblon ligand with a linker, which is a useful precursor for synthesis of PROTAC degraders. Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. PROTAC degraders are usually heterobifunctional small molecules consisting of two ligands joined by a linker: one ligand recruits and binds a protein of interest (POI) while the other recruits and binds an E3 ubiquitin ligase. Simultaneous binding of the POI and ligase by the PROTAC induces ubiquitylation of the POI and its subsequent degradation by the ubiquitin–proteasome system (UPS), after which the PROTAC is recycled to target another copy of the POI.
