This brings together the expertise of Professor Alessio Ciulli, one of the pioneers in the field of Proteolysis targeting chimeras (PROTACs), based in the School of Life Sciences at Dundee, with Boehringer Ingelheim's pharmaceutical expertise and commitment to bring innovative medicines to patients with cancer.
PROTACs represent a new class of drug candidates with the potential to tackle compelling cancer targets which have failed traditional medicinal chemistry approaches.
They work by harnessing the cell's natural disposal system (the ubiquitin-proteasome). Candidate disease-causing proteins are labelled as "expired" proteins which the proteasome then shreds.
Since the initiation of the collaboration in 2016 and a significant expansion in 2018, the application of PROTACs has grown dramatically.
However, designing PROTACs remains challenging and largely empirical in nature, hindering faster progress in the field.
The partners have thus developed a structure-based design approach as a solid basis to accelerate further development. In addition, to boost PROTAC research around the world, Boehringer Ingelheim has made the protein degrader compound MZ-1, developed at the University of Dundee, freely available through its opnMe portal in 2018.
Further PROTAC molecules are considered for release on opnMe based on the success of this initiative.
The joint team has reported recent progress in a number of scientific publications, including most recently in the journal Nature Chemical Biology. This publication highlights their approach to use 3-dimensional pictures at atomic resolution to design highly potent and selective drug candidates.
The new approach has yielded the first PROTAC which shreds SMARCA2, a protein that drives the tumors of more than 20,000 new patients with cancer each year and for which drug discovery approaches have otherwise been unsuccessful to date.
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