Our research

G protein-coupled receptors (GPCRs) are a class of membrane-bound receptors that regulate a wide range of physiological processes and thus have an immense potential as drug targets. Although an impressive third of current therapies target GPCRs, only about 20% of the approximately 900 GPCRs are targeted. Additionally, drug discovery programs involving GPCRs are characterised by a high attrition rate, whilst clinically approved GPCR drugs are often associated with severe side effects. This disappointing progress has been largely attributed to the inadequate fundamental understanding of these receptors. Therefore, there is a need to improve our knowledge of these receptors on an atomic level.

In the last two decades, technological advances in the expression, purification and structure determination of GPCRs has greatly advanced GRCR pharmacology and thereby revealed that the structure and activation of GPCRs is far more complex than previously recognised. This has opened new avenues for medicinal chemists and led to the development of novel concepts, such as allostery, biased agonism and oligomerisation of receptors. Chemical probes are crucial to study these concepts, as well as other functional or structural features of receptors, as these probes have unique properties that allow for example the stabilisation or visualisation of a receptor.