Lead Discovery for Targeting G Protein-coupled Receptors

G protein-coupled receptors (GPCRs) control a plethora of key physiological functions in every cell of an organism. GPCRs are therefore involved in many diseases, since altered ligand or receptor levels, and genetic or epigenetic modifications can lead to GPCR dysfunction and hence a pathophysiological phenotype. About one third of currently marketed drugs target GPCRs. The human genome contains 720-800 predicted GPCRs, and about half of them respond to olfactory/sensory signals, whereas the others are known or predicted to be activated by endogenous ligands and many of these represent potential drug targets. 77% of these non-sensory GPCRs belong to the class A (rhodopsin-like) family, whereas 14% represent class B (secretin-like) GPCRs,