Hertfordshire-based Heptares is a drug discovery company creating new medicines targeting G-protein-coupled receptors (GPCRs). Responsible for transmitting chemical signals into a variety of different cell types, GPCRs represent the single most important family of drug targets in the human body because they are central to so many biological processes.

There are over 700 GPCRs encoded in the human genome and as many as 75 of these have clinical validation, presenting a wide range of opportunities as therapeutic targets in areas including cancer, diabetes, central nervous system disorders, obesity and pain. However, GPCRs become extremely unstable when removed from cell membranes, making them incredibly difficult to crystallise. To overcome this, Heptares has developed a new technology, called StaR® (Stabilised Receptor), which allows the selection of stable, functionally relevant, purified conformations of target GPCRs that retain their expected drug-binding characteristics.

Image: Dr Andrew Doré, Senior Scientist at Heptares, using Diamond’s Microfocus MX beamline (I24).

“We used Diamond to solve the 3D structure of adenosine A2A, a GPCR linked to Parkinson’s disease, which we had stabilised using our StaR® technology,” says Dr Andrew Doré, Senior Scientist at Heptares. “Being able to generate co-crystal structures of our lead series helped the medicinal chemists to develop a highly optimised drug candidate which will now be developed by Shire Pharmaceuticals.”

Although a commercial company, accessing Diamond via the proprietary route, Heptares also publish some of their structural data in peer-reviewed journals. “We sometimes publish our findings once a drug has been discovered and taken forward,” explains Andrew. “The structural knowledge gained from GPCRs could be useful in related studies and will further our general understanding of this important family of membrane proteins.”