Boehringer Ingelheim has teamed up with the University of Dundee to develop proteolysis-targeting chimeric molecules (PROTACs), a new class of drugs designed to degrade proteins. The idea is to leverage the cell’s own disposal system to eliminate proteins involved in the development of diseases including cancer.
PROTACs are designed to bind to a ubiquitin ligase and a protein simultaneously, triggering a process that leads to the degradation of the target. With RNAi screens identifying proteins such as the bromodomain and extraterminal (BET) domain family as playing a role in cancers, respiratory diseases and other conditions, PROTACs are seen as a platform technology with the potential to be applied across a range of therapeutic areas.
The University of Dundee is at the forefront of turning this idea into reality. “We believe our approach has the potential to fundamentally transform how we tackle protein targets to fight disease,” University of Dundee’s Alessio Ciulli said in a statement.
In teaming up with Ciulli, Clive Wood, SVP of discovery research at Boehringer, has allied his firm with a pioneer in PROTAC research at a time when the nascent niche appears to have resolved some of the issues that have stymied its progress to date.
The term PROTAC was coined in the early 2000s, but for most of the field’s history researchers have struggled to find small molecules that bind to ubiquitin ligases with the affinity and specificity needed for drug candidates. That has started to change over the past two years. Papers published by researchers at GlaxoSmithKline ($GSK)--which has a protein degradation team at its Stevenage, U.K. site--Yale University, Dana-Farber Cancer Institute and the University of Dundee have shifted perceptions of the potential of PROTACs.
Boehringer has responded by teaming up with the University of Dundee, specifically Ciulli and his team. Research published over the past year suggest Ciulli’s team can selectively target BRD4, which has been linked to acute myeloid leukemia, ovarian carcinoma and chronic obstructive pulmonary disease. The idea now is to pair this research-stage breakthrough with Boehringer’s drug discovery machinery.
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