European alliance to advance proximity-induced drug modalities

Experts from Dundee’s Centre for Targeted Protein Degradation (CeTPD) have united with counterparts from Goethe University Frankfurt in Germany, IRB Barcelona in Spain, CeMM and AITHYRA in Vienna, Austria, and EPFL Lausanne in Switzerland to harness the concept of bringing molecules into close proximity to target disease-relevant proteins, many of which are currently considered undruggable. The proposal appears in an article in the journal, Molecular Cell.

Proximity-inducing drug modalities, such as proteolysis-targeting chimeras (PROTACs) and molecular glue degraders, function by reprograming the cellular machinery to modify or eliminate disease-causing proteins. Originating from the concept of harnessing the cell’s own waste-disposal system to direct specific proteins toward degradation, these approaches have transformed the way scientists approach targeting disease mechanisms. Unlike traditional inhibitors, proximity-inducing drugs can remove entire proteins, and the concept has meanwhile expanded beyond degradation to the broader rewiring of cellular pathways. 

In the United Kingdom, the Centre for Targeted Protein Degradation (CeTPD), led by Professor Alessio Ciulli FRS, one of the pioneers of PROTACs and proximity-based protein degradation, drives the development of this revolutionary class of drugs. Part of the University of Dundee’s School of Life Sciences, the CeTPD has grown to a team of 70 composed of three Principal Investigators and their academic groups that innovate fundamental research in TPD and induced-proximity pharmacology. 

The Centre has built a broad international network of partners and collaborators, securing substantive funding from public, charities and the biopharma industry to establish multidisciplinary teams to translate the innovation through drug discovery programs. Example of these are partnerships with Boehringer Ingelheim and Eisai design to advance degrader drugs in oncology, and Amphista therapeutics, a spinout from the Ciulli lab, to develop next-generation TPD therapeutics.

“Proximity-inducing strategies are transforming how we think and execute small-molecule drug development,” says Professor Alessio Ciulli, CeTPD’s founder and Director and one of the authors of the perspective. 

“Leveraging our track-record and integrating efforts with other internationally leading institutions will accelerate the pace of innovation in the field. Our vision goes beyond establishing an academic network and aspires to build meaningful links more broadly with industry, investors and the wider ecosystem.”

The article 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. It also discusses how AI and machine learning have the potential to transform and accelerate discoveries in this field.  Proximity-induced drugs can address biological targets that are inaccessible to conventional inhibitors and hold promise for the treatment of a range of “undruggable” diseases. 

The authors of the article emphasise the foundational role of academia in advancing this field and call for tighter academic-industry collaboration to unlock its full therapeutic potential. The research centres in Vienna, Dundee, Barcelona, Frankfurt, and Lausanne have built complementary expertise in medicinal chemistry, structural biology, biophysics, cell biology and computational methods. Although collaborations already exist, they are often limited in scope and duration. 

The proposed European Alliance aims to pool expertise, infrastructure, and digital platforms across Europe. It would facilitate access to and coordinate the benchmarking of technologies, improve the integration of laboratory-driven and computational discovery approaches, and develop 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. 

“The pre-competitive space is where academic freedom, technology innovation, and biopharma experience can reinforce one another,” says Professor Ivan Đikić, a co-author of the article from Goethe University Frankfurt.

“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.”