European alliance to advance proximity-induced drug modalities

Proximity-inducing drugs, such as proteolysis-targeting chimeras (PROTACs) and molecular glue degraders, work by reprograming the cell’s own machinery to modify or eliminate disease-causing proteins. Unlike traditional inhibitors, proximity-inducing drugs can remove entire proteins, but the concept has now moved on to the broader rewiring of cellular pathways.

Proximity-inducing drugs can reach biological targets that are inaccessible to conventional inhibitors, meaning that they can be used to treat a range of diseases currently considered “undruggable”.

Now, scientists from EPFL, Goethe University Frankfurt, IRB Barcelona, CeMM and AITHYRA in Vienna, and the University of Dundee have published a Perspective in the journal Molecular Cell calling for the creation of a European Alliance to accelerate the development of proximity-induced drug modalities.

The Perspective highlights recent scientific breakthroughs, including the evolution of PROTACs from concept to clinic, rational design of molecular glues, and novel strategies to redirect cellular degradation machinery.

The scientists also discuss how AI and machine learning (ML) can transform and accelerate discoveries in the field. Such tools are helping scientists predict which molecules might work together, design new drug candidates, and analyze large experimental datasets. Predictive models such as the protein-designing AlphaFold can speed up discovery and open the door to treating targets that were once considered out of reach.

The authors point out that European research hubs have developed complementary expertise in medicinal chemistry, structural biology, biophysics, cell biology, and computational methods. They argue that closer collaboration, supported by both public and private funding, will be essential to unlock the full potential of these modalities.

The proposed European Alliance would pool expertise, infrastructure, and digital platforms across Europe. It would coordinate benchmarking of technologies, improve the integration of laboratory-driven and computational discovery approaches, and develop new, in vivo models to address delivery and safety challenges. The authors propose to seek both public and private funding to connect existing European hubs with international partners, including pharmaceutical companies, biotechnology firms, and technology developers.

“Proximity-inducing molecules are an exciting opportunity in drug discovery, and our work at EPFL combines expertise in chemistry, biology, computer science and medicine to explore their full potential,” says Nicolas Thomä, professor at EPFL’s School of Life Sciences and co-author of the Perspective.