Characterization of binding affinity of CJ-023,423 for human prostanoid EP4 receptor.
In order to characterize the receptor binding pharmacology of CJ-023,423, a potent and selective EP4 antagonist, we performed a radioligand receptor binding assay under various assay conditions. An acidic (pH 6) and hypotonic buffer is a conventional, well-known buffer for prostaglandin E2 receptor binding assays. CJ-023,423 showed moderate binding affinity for human EP4 receptor under conventional buffer conditions. However, its binding affinity was greatly increased under neutral (pH 7.4) and isotonic buffer conditions. In this report, the binding mechanism between CJ-023,423 and human EP4 receptor is discussed based on the binding affinities determined under various assay conditions.
Murase
Akio
A
Discovery Biology Research, Pfizer Global Research and Development, Aichi, Japan.
Nakao
Kazunari
K
Takada
Junji
J
D001667:Binding, Competitive; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011485:Protein Binding; D011869:Radioligand Assay; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides / Q000494:pharmacology*; D007093:Imidazoles; D011725:Pyridines; D013453:Sulfonylurea Compounds; D000096926:Benzenesulfonamides
D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; C545650:PTGER4 protein, human; C522837:grapiprant; D007093:Imidazoles; D011725:Pyridines; D013453:Sulfonylurea Compounds; D000096926:Benzenesulfonamides