Discovery Technologies

Significance of GPCRs

GPCRs, which are cell surface membrane proteins involved in mediating both sensory and nonsensory functions, comprise one of the largest families of proteins in the genomes of multicellular organisms. The GPCR family represents an important source of drug discovery. GPCR-targeted drugs account for nearly 40% of all drugs sold worldwide.

Although GPCRs form a super-family of receptors, individual GPCRs display a high degree of specificity and affinity for the functionally active molecules, or ligands, that bind to a given receptor. When activated by its ligand, the GPCR interacts with intracellular G proteins, resulting in a cascade of signaling events inside the cell that ultimately leads to the particular function linked to the receptor. There are 370 non-sensory GPCRs with known ligands and 167 of them are drug targets – 108 for FDA approved medications and 66 for molecules in clinical trials.

Without a known ligand, there is no template for medicinal chemistry and no way to identify the GPCR’s signaling pathway. This means that drugs are very difficult to develop against orphan GPCRs. Only 7 of the 116 orphan GPCRs have had a drug developed against them. “Unlocking” an orphan GPCR by identifying one or more of its respective ligands can lead to the development of drugs that act at the previously undruggable receptor.