PROTACs are traditionally conceived as bifunctional, i.e. composed of two ligands joined by a linker, forming a ternary complex consisting of Target Protein:PROTAC:E3 ligase, resulting in ubiquitination and subsequent degradation of the target protein via the proteasome . PROTACs have successfully been applied to degrade a wide spectrum of protein targets including nuclear , cytoplasmic , membrane-bound , and multi-pass transmembrane proteins , most commonly by recruiting either the von Hippel-Lindau (VHL) or cereblon (CRBN) E3 ligases.