Informed development of drugs acting at family B G protein-coupled receptors.
Rational refinement and development of receptor-active ligands can come from high-resolution insights into the structures of these potential drug targets. Structural insights for Family A G protein-coupled receptors (GPCRs) have been advanced substantially with the recently reported crystal structure of the intact beta(2)-adrenergic receptor. While high-resolution structural insights for Family B GPCRs are also advancing, this is currently limited to the functionally important extracellular amino-terminal tail domain of those receptors. The current report describes how these structures can provide leads for the development of small-molecule agonist drugs acting at Family B GPCRs. Endogenous agonist activity within the amino terminus of these receptors could be key for the development of such drugs.
Miller
Laurence J
LJ
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, USA. miller@mayo.edu
D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D012633:Secretin / Q000378:metabolism
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D012633:Secretin