Boehringer Ingelheim, University of Dundee collaboration for newer class of drug development – proteolysis-targeting chimeras (PROTACs)

Boehringer Ingelheim and the University of Dundee will join forces in an exciting collaboration with the aim to develop a novel class of medicines that target disease causing proteins for degradation. The collaboration brings together the expertise of Dr Alessio Ciulli, one of the pioneers in the field of proteolysis-targeting chimeras (PROTACs) and based in the School of Life Sciences at Dundee, with Boehringer Ingelheim’s expertise in drug discovery and clinical development of new therapeutic agents.

PROTACs are designed to harness the cell’s natural disposal system (the ubiquitin-proteasome) to specifically remove disease causing proteins. They do this by triggering the labelling of these as “expired” proteins, which the proteasome then removes. PROTACs are anticipated to be broadly applicable to therapeutic areas as diverse as oncology, immunology and respiratory diseases. It opens up opportunities to target disease mechanisms that have been difficult to reach with existing modalities.

To trigger the degradation of target proteins, PROTACs are made of a moiety that binds the target and a moiety that binds a ubiquitin ligase enzyme, and as a result they are likely to exceed the size of conventional oral drug molecules. The design of such “medium sized” drug molecules represents a considerable challenge.