G-Protein-Coupled Receptor/GPCR Ligands as Drug Target

G-Protein-Coupled Receptor/GPCR Ligands as Drug Target Background

G-protein-coupled receptor/GPCR ligands are compounds that bind to a GPCRs. These may be conceptualized as "keys" that fit into a specific "lock" on the cell surface, the latter being the receptor, to modify cellular activity at the biophysical, biochemical, and/or genomic level.

The complex signaling pathways modulated by G-protein-coupled receptors/GPCRs offer a variety of potential drug targets. GPCRs are coupled to various members of the G protein superfamily, so named because of their functional dependence on the hydrolysis of the purine nucleotide, GTP, for activity.

GPCRs in mammals are classified into five main families, named Glutamate, Rhodopsin, Adhesion, Frizzled, and Secretin according to the GRAFS classification.

GPCRs regulate physiological responses to a variety of stimuli that include endogenous ligands such as biogenic amines, peptides, glycoproteins, lipids, nucleotides, Ca2+ ions, and various exogenous ligands for sensory perception such as odorants, pheromones, and even photons.

As a consequence, these receptors mediate multiple physiological processes such as neurotransmission, cellular metabolism, secretion, cellular differentiation, growth, inflammatory, and immune responses.

It is estimated that ~50% of clinically prescribed drugs and 25 of the 100 top selling drugs target GPCRs. Yet, only a small fraction of all GPCRs are presently targeted by drugs.