133487Development of a novel fragment screening platform for G protein-Coupled ReceptorsClosedFeasibility StudiesInnovate UK"G-protein coupled receptors (GPCRs) are proteins found on the surface of cells: they detect molecules outside the cell and consequently activate internal signalling pathways that mediate cellular responses. GPCRs are one of the most important human drug target classes, and are addressed by 25-30% of marketed drugs. Many GPCRs that are known to have disease relevance remain undrugged, highlighting the ongoing importance of this target group in the search for new medicines. Historically, methods of studying GPCRs have been very successful at identifying and profiling chemicals that modulate their function. However, these empirical approaches have tended to find compounds that are only partially selective for the desired target, because they give insufficiently precise information to drive rational drug design towards highly-specific agents. Recently it has been shown that making mutated forms of some GPCRs makes them stable enough to use structural and biophysical methods that can allow the design of more selective drugs, and unlock traditionally undruggable targets of this class. But this is a difficult and lengthy task requiring extensive method development for each individual target. Domainex has embraced a new method for starting drug discovery projects using a biophysical technique called MicroScale Thermophoresis (MST). This proposal will test the feasibility of using this approach on GPCRs, in order to establish a generic platform that would enable work any purified GPCR without the need for stabilising mutations. We will use a new method developed in a UK university to stabilise the GPCR. If successful, this project will lead to a new service that Domainex can offer to prospective clients. This will provide the Company with new revenues, and facilitate our clients' research projects meaning that better drugs will get to patients, faster."