GPCRs are expressed in every type of cell in the body and play a critical role in linking messages from extracellular ligands to signalling pathways within the cell, between cells and between organ systems. GPCRs are drug targets in all major therapeutic areas and are the site of action of 25-30% of current drugs, some with multi-billion dollar annual sales.

The superfamily of GPCRs is defined by having 7-transmembrane spanning domains. These are activated by a wide variety of ligand types including protein and peptide hormones, peptide and small molecule neurotransmitters, metabolites, bacterial products and light.

Within the GPCR superfamily are a number of subfamilies that are linked by extensive amino acid similarity. These are:

Family A receptors: These include many neurotransmitter receptors, such as dopamine and adrenaline, peptide receptors such as opioid and neurokinin receptors, glycoprotein hormone receptors such as follicle stimulating hormone, and chemokine receptors such as CCR5, which is a target for HIV therapy.

Family B receptors: This family is activated by large peptide and protein ligands and plays a critical role in physiological processes such as appetite regulation, insulin signalling, stress and pain. The receptors are activated by ligands including glucagon-like peptide, calcitonin gene related peptide and corticotrophin-releasing hormone. Although many of these receptors are validated as disease targets through the use of protein therapeutics, to date few small molecule drugs are known to target this class.

Family C (metabotropic) receptors: This family is unusual in that it has very large extracellular domains. However, many of the drugs that are being developed for this class of receptors actually bind to the transmembrane domain and act as allosteric modulators. The metabotropic glutamate receptors are the largest subfamily within Family C and are important drug targets for a variety of neurological and psychiatric diseases.