Scientists from six leading European research institutions have published a perspective in Molecular Cell calling for the creation of a European Alliance to accelerate the development of proximity-induced drug modalities. The collaborative effort, involving researchers from Goethe University Frankfurt, IRB Barcelona, CeMM and AITHYRA in Vienna, the University of Dundee, and EPFL Lausanne, aims to advance therapeutic approaches that target previously "undruggable" proteins.
Revolutionary Approach to Drug Development
Proximity-inducing drug modalities, including proteolysis-targeting chimeras (PROTACs) and molecular glue degraders, represent a paradigm shift in pharmaceutical development. These therapeutics function by reprogramming cellular machinery to modify or eliminate disease-causing proteins, harnessing the cell's own waste-disposal system to direct specific proteins toward degradation.
"Proximity-inducing strategies could prove to be game-changers for drug development," says Ivan Đikić, PROXIDRUGS speaker and Goethe University professor. "Integrating our national efforts with other internationally leading institutions will accelerate the pace of innovation. Our vision goes beyond building academic networks in fostering broad industry collaboration."
Unlike traditional inhibitors that block protein function, proximity-inducing drugs can remove entire proteins from cells. The concept has expanded beyond degradation to encompass broader rewiring of cellular pathways, opening new therapeutic possibilities for targets that were previously considered inaccessible to conventional drug approaches.
Building on German Success
The initiative builds upon the success of Germany's PROXIDRUGS Cluster4Future, led by Goethe University Frankfurt. Since October 2021, PROXIDRUGS has secured annual funding of €5 million from the German Federal Ministry of Research, Technology and Space (BMFTR), establishing a broad national network of academic and industrial partners.
Goethe University contributes decade-long expertise in researching cellular waste disposal pathways, particularly the ubiquitin-proteasome and autophagy systems. The institution also houses the newly founded Frankfurt Center for Emerging Therapeutics (FCET), an innovation hub for interdisciplinary research that enables rapid technology transfer.
Comprehensive European Collaboration
The published perspective outlines 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 authors also discuss how artificial intelligence and machine learning have the potential to transform and accelerate discoveries in this field.
The research centers in Vienna, Dundee, Barcelona, Frankfurt, and Lausanne have developed complementary expertise spanning medicinal chemistry, structural biology, biophysics, cell biology, and computational methods. While collaborations already exist between these institutions, they are often limited in scope and duration.
Alliance Objectives and Implementation
The proposed European Alliance aims to pool expertise, infrastructure, and digital platforms across Europe. Key objectives include facilitating access to and coordinating the benchmarking of technologies, improving integration of laboratory-driven and computational discovery approaches, and developing in vivo models to address delivery and safety challenges.
The authors propose seeking both public and private funding to connect existing European hubs with international partners, including pharmaceutical companies, biotechnology firms, and technology developers. The alliance would operate in the pre-competitive space where academic freedom, methodological innovation, and industrial experience can reinforce one another.
"The pre-competitive space is where academic freedom, methodological innovation, and industrial experience can reinforce one another," explains Đikić. "This is where an alliance can deliver the greatest impact, motivate other partners to join and increase the likelihood of novel concepts progressing efficiently from lab to life."
Addressing Undruggable Targets
Proximity-induced drugs hold particular promise for treating diseases involving "undruggable" targets—biological proteins that are inaccessible to conventional inhibitors. These therapeutics can address targets that have historically been challenging for traditional drug development approaches, potentially expanding treatment options for various diseases.
The perspective emphasizes the foundational role of academia in advancing this field and calls for tighter academic-industry collaboration to unlock the full therapeutic potential of proximity-induced drug modalities. The authors envision the alliance facilitating resource sharing, accelerating early-stage drug discovery, and training the next generation of scientists to ensure faster translation of breakthroughs from laboratory to clinic.
