Beyond PROTACs and the proteasome: broadening the TAC toolbox

The idea of sending disease-driving proteins to the cell’s garbage can is only the first act in a field that now centers around targeted degradation. In the sequel, researchers are extending the principle to other types of cellular machinery, with iterations that promise access to an even broader range of targets, and to enzyme functions beyond protein degradation.

These next-generation targeting chimeras, or “TACs,” are opening the door to therapies that activate, deactivate or protect targets of interest. But the first translational challenges are likely to be getting the right bioavailability and kinetics...