The mechanism of action and clinical value of PROTACs: A graphical review.

The use of small molecule drugs to inhibit active protein targets has revolutionised the treatment options for many diseases in the past 30 years. The greatly improved pharmacokinetic properties of modern drugs combined with enhanced cell permeability and oral bioavailability has made these molecules ideal for reaching protein targets of interest in cells and inhibiting disease-driven signalling pathways. However, these small molecule drugs have several limitations which have opened the doors for the development of a new class of compounds, known as proteolysis targeting chimeras (PROTACs). These next generation drugs actively and specifically degrade designated protein targets and hold the potential to greatly expand the druggable genome, including previously drug-resistant targets.