Building the Next Generation of GPCR-Targeting Drugs

If you’re going to hunt for new drugs, targeting G-protein coupled receptors (GPCRs) would seem a good starting point. One third of marketed drugs hit this group of cell-membrane bound receptors, which are involved in almost every possible biological system. Activated by a wide range of ligands outside the cell that link onto the GPCR’s extracellular component, GPCRs mediate a variety of cellular responses via signal transduction pathways inside the cell, usually via activation of a G-protein. Many of the body’s hormones bind to GPCRs, and these receptors also reside in a host of different tissue types. Drugs targeting GPCRs therefore span most therapy areas, specialist or primary care, and may be small molecules, peptides, or large proteins. Just a few examples of GPCR-targeting drugs include household names such as loratadine (Claritin), fluoxetine (Prozac), and the triptans, including for instance sumatriptan (Imitrex/Imigran).

Yet there’s plenty of untapped potential, too. Scientists have identified more than 350 non-sensory GPCRs (the sensory ones, involved in...