Continued discovery of ligands for G protein-coupled receptors.
G protein-coupled receptors are under intense scrutiny as potential targets of drug research, which stems mostly from the sheer size and diversity of this receptor family as well as the recognized high levels of specificity and sensitivity attainable by drugs targeting these receptors. The continued discovery of genes encoding G protein-coupled receptors has provided an extensive reserve of potential therapeutic targets. However, testing experimental therapeutic agents at these receptors requires a high degree of receptor characterization, beginning with the identity of an endogenous ligand. Often, low levels of sequence identity of a newly identified receptor to previously characterized receptors preclude the prompt identification of a ligand. In such cases, innovative techniques commonly referred to as reverse pharmacology have been employed to ascertain the ligand's identity for these "orphan" receptors. To date over 30 endogenous ligands, both novel and previously known, have been paired with orphan G protein-coupled receptors. Here, we briefly summarize the recent identification of neuropeptides W and B and carboxylic acid anions for their respective receptors GPR7, GPR8 and GPR40, GPR41, GPR43.
Lee
Dennis K
DK
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
George
Susan R
SR
O'Dowd
Brian F
BF
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008024:Ligands; D009479:Neuropeptides / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D008024:Ligands; C467731:NPW protein, human; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled