RT Journal Article
SR Electronic
T1 Identification of a Potent and Selective Synthetic Agonist at the CRTH2 Receptor
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1834
OP 1839
DO 10.1124/mol.104.009068
VO 67
IS 6
A1 Gervais, François G.
A1 Morello, Jean-Pierre
A1 Beaulieu, Christian
A1 Sawyer, Nicole
A1 Denis, Danielle
A1 Greig, Gillian
A1 Malebranche, A. Daniel
A1 O'Neill, Gary P.
YR 2005
UL http://molpharm.aspetjournals.org/content/67/6/1834.abstract
AB The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is a G protein-coupled receptor whose function in vivo has been incompletely characterized. One of the reasons is that its current known ligands, prostaglandin D2 and some of its metabolites, have either poor selectivity for CRTH2 or are metabolically unstable in vivo. In this study, we describe the biological and pharmacological properties of L-888,607, the first synthetic potent and selective CRTH2 agonist. We show that L-888,607 exhibits 1) subnanomolar affinity for the human CRTH2 receptor, 2) high selectivity over all other prostanoid receptors and other receptors tested, 3) agonistic activity on recombinant and endogenously expressed CRTH2 receptor, and 4) relative stability in vivo. L-888,607 thus represents a suitable tool to investigate the in vivo function of CRTH2.