PROTAC logic continues to evolve

Academics and companies are developing PROTAC-adjacent methods that overcome some of the hurdles of the modality such as complex design, poor bioavailability due to large size, and limitation to intracellular targets.

The TAC field took off with modular compounds known as proteolysis targeting chimeras (PROTACs), which ubiquitinate targets and send them to the proteasome for degradation. These bivalent structures use a linker to connect separate ligands for a target of interest and an E3 ligase...