Boehringer Ingelheim and University of Dundee Highlight Successful PROTAC Drug Discovery Program and Extend Their Ongoing Anti-Cancer Alliance
Following the success of their ongoing alliance, Boehringer Ingelheim and the University of Dundee extend their collaboration to develop new medicines that target and destroy key cancer causing proteins. 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.
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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.
“PROTACs are a disruptive therapeutic modality which are bringing previously deemed undruggable targets within reach. Our collaboration will continue to work to bring this new class of medicines to patients,” said Darryl B. McConnell, Ph.D., Senior Vice President and Research Site Head, Boehringer Ingelheim, Vienna, Austria. “The joint team is making rapid progress and have successfully reached the first collaboration milestone setting a solid basis for achieving our goals.”
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.
“Our joint publication is a leading example of translating the detailed understanding we are developing of how PROTACs work, to craft degrader molecules that effectively tackle previously ‘undruggable’ targets”, said Alessio Ciulli, Ph.D., Chair of Chemical and Structural Biology at the University of Dundee, and winner of the 2016 RSC Capps Green Zomaya Award for medicinal chemistry. “The expansion marks an important milestone in the development of our alliance. It enables the joint team to drive the next phase of degrading highly-prized cancer targets previously intractable via other approaches”
Boehringer Ingelheim is focusing on developing innovative new treatment approaches providing outstanding value for patients. To achieve this, the company is increasing its commitment to external innovation, and is working with top partners from academia and industry worldwide. A growing network of academic collaborations reflects the company’s focus on emerging science that could open new avenues leading to the breakthrough medications of the future.
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