A combined investment of £11.2m that includes a prosperity partnership grant from the Engineering and Physical Sciences Research Council (EPSRC) and funds from AstraZeneca (AZ) has enabled researchers at the Francis Crick Institute, Imperial College London and AZ to discover new 'molecular glues' to treat multiple diseases.

Widely used as protein degraders, molecular glues bring together proteins that would not usually interrelate. The glues manage the modification and degradation of disease-causing target proteins by redirecting them to the cell's natural waste disposal system.

By facilitating the interaction between target protein and a cellular enzyme, the target protein is deactivated or broken down by additional proteins that are recruited by the enzyme.

Group leader at the Crick Institute, Ed Tate, said: “Challenges arise when we can’t find a small molecule with the ability to interact with certain proteins.

"If we can redirect these harmful proteins towards the cell’s own waste disposal system, we could more effectively treat different diseases like cancer."

The project will unify 12 postdoctoral researchers from contrasting scientific specialities, as well as three PhD students. Scientists at Imperial College and AZ will work across eight different laboratories and scientific technology platforms at the Crick.

The team will develop a rule book for the discovery of new molecular glue degraders, with a focus on targeting ‘undruggable’ proteins with conventional treatment options.

Vice president at AZ, Steve Fawell, said: “Through this work, we have the opportunity to reach important oncology targets that were previously considered undruggable using traditional approaches. We are delighted to collaborate on this innovative research, which has the potential to bring new medicines to patients who need them the most.”

Associate research director at the Crick Institute, Julian Downward, said: “In certain cancers like lung and pancreatic, there are tumour-promoting, disordered proteins that we have struggled specifically [to] target with traditional drug discovery methods. These proteins will be an early focus of the project as we combine the expertise of chemical and cancer biologists.

"There are also a number of other health conditions caused by the accumulation of harmful proteins, like neurodegenerative diseases where protein plaques in the brain slowly lead to cell death.”

Through new innovative research, the collaboration between the Crick, Imperial College London and AZ will enhance developments for treating diseases by opening up new, unique opportunities to tackle some of the biggest health challenges being faced globally that traditional approaches would not have been able to achieve.

Director of Partnerships at EPSRC, Dr Andrew Bourne, commented: "These new projects showcase the breadth of research and innovation in the UK, covering a wider range of sectors, and support the UK’s ambitions to be a science superpower and an innovation nation.”

Reference：
https://www.pmlive.com/pharma_news/crick_institute_announces_new_molecular_glue_discovery_to_treat_different_diseases_1491923