Agonists Neutral Antagonists And Inverse Agonists

G protein-coupled receptors (GPCRs) represent the largest superfamily of cell surface receptors, with approximately 800 functioning receptor proteins encoded within the human genome. Conserved structural GPCR motifs include seven a-helical transmembrane (TM) domains of approximately 25-35 amino acids, an extracellular N-terminal domain, and an intracellular C-terminal domain. GPCR TM domains are relatively conserved and form the basis of the GPCR classification system of GPCRs into six families [1]. Although some structural motifs are highly conserved, sufficient sequence variability exists within the GPCR superfamily to allow selective accommodation of a vast array of endogenous stimuli, including ions, organic odorants, amines, peptides, proteins, lipids, nucleotides, and photons [1]. In addition, the identification of natural and synthetic compounds found to either mimic or block the actions of endogenous agonists continually increases the diversity of GPCR ligands in the chemical space. The type and strength of interaction a compound has with its receptor is driven both by the chemical structure of the ligand and the nature of the receptor epitopes available within the binding pocket. Classical receptor--igand interactions define two important system-independent properties of a compound: affinity and intrinsic efficacy.

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