Much of the current research effort undertaken within the pharmaceutical industry today is focussed on G protein-coupled receptors (GPCRs). These are a very large family of cell surface receptors that share a common topology, characterized by seven transmembrane spanning domains. They are important in cellular communication, generally effected by binding of structurally diverse ligands, for example, amine neurotransmitters or peptides, which leads to signal transduction through the receptor to intracellular associated G proteins and beyond.

So, why the high level of interest? An overwhelming reason is because they have a proven history of being excellent drug targets. Early drugs, for example, morphine, beta-blockers, anti-psychotics, anti-ulcers, were developed without knowing the molecular identity of the receptor (perhaps receptors) that the compounds were interacting with. It can now be established that in the last few decades over a hundred drugs have been launched that are directed at them spanning a wide range of diseases. Another reason underlies much of what will be heard today. The rapid sequencing of the human genome, much of which was completed in draft form only in the past couple of years, has enabled us to go hunting for all the family members, much faster than anyone would have dared to believe even a few years ago.

We can now start to ask questions, many of which will be answered in the lectures today. How did we go about trying to identify all the receptors and what makes us believe they are GPCRs? Do we know what activates them all, i.e. do we know the ligands? No, we do not. So-called unpaired receptors are termed orphans. How do we go about finding the natural ligands? If we want to make unnatural ligands, which we do for many reasons, how do we do this and how do we screen the receptors? How do we know if the orphan receptors are biologically relevant to disease? Simply asked questions but not easily answered. I'm sure this meeting will generate many more.

Malcolm Duckworth
(Chairman, Society for Medicines Research)