The pyrazolone originally reported to be a formyl peptide receptor (FPR) 2/ALX-selective agonist is instead an FPR1 and FPR2/ALX dual agonist.
A pyrazolone compound acting as a formyl peptide receptor (FPR) 2/ALX-selective agonist has been reported, but its pharmacological activities on human FPRs (hFPRs) and mouse FPRs (mFprs) have not been well demonstrated. In this study, we found that this compound, designated as compound A, induced concentration-dependent calcium flux not only in Chinese hamster ovary (CHO) cells expressing hFPR2/ALX but also in cells expressing hFPR1, mFpr1, or mFpr2. It also induced the receptor internalization of hFPR1 and hFPR2/ALX and, accordingly, induced calcium influx and chemotactic responses in both human and mouse neutrophils. Our study revealed that compound A is in fact an FPR1 and FPR2/ALX dual agonist.
Sogawa
Yoshitaka
Y
Biological Research Laboratories III, Daiichi Sankyo Co., Ltd., Japan.
Shimizugawa
Akiko
A
Ohyama
Takao
T
Maeda
Hiroaki
H
Hirahara
Kazuki
K
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D047069:Pyrazolones / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000819:agonists*; D044067:Receptors, Lipoxin / Q000819:agonists*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C469986:FPR1 protein, human; C105101:FPR2 protein, human; C547175:N-(4-chlorophenyl)-N'-(5-isopropyl-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)urea; D047069:Pyrazolones; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D014508:Urea; D002118:Calcium