research & technology
Untapped potential in the GPCR superfamily
G protein-coupled receptors (GPCRs) make up the largest single protein family class in the human genome. Their key function is the conversion of signals from the outside of the cell to the inside (signal transduction). This role in the body’s communication system makes them critical in many physiological processes; thus, they have become the largest single class of drug targets in multiple therapeutic areas. Although marketed drugs are available for many different receptors, not all GPCR receptors are tractable to drug discovery with traditional screening and pharmacological evaluation methods. In addition:
- GPCRs remain a formidable challenge from a drug discovery perspective in the development of orally available small molecule drugs targeting lipid and peptide class A receptors and the glucagon class B receptors.
- The discovery of novel allosteric binding sites that are typically not conserved between related receptor family members allows for the design of drug candidates that bind to these sites and exhibit improved receptor specificity properties. Such properties may diminish off-target safety concerns.
- Biased ligand signal transduction is a new and exciting area of development where cell based screens coupled with structure and biophysical ligand screening can play a significant role towards the development of novel therapeutics.