3-(4-chlorophenyl)-1-(1-methyl-3-oxo-2-phenyl-5-propan-2-ylpyrazol-4-yl)urea (Cpd43) is a low MW compound synthesized as an agonist for FPR2 and has been shown to have this function in human leukocytes. In vivo, Cpd43 exerts anti-inflammatory effects in murine ear inflammation and air-pouch models, which require FPR2 has agonistic activities for human FPR1 and FPR2/ALX. The EC50 values of Cpd43 for FPR1 and FPR2/ALX were 65 nM and 22 nM, respectively, in the aequorin assay that measured calcium mobilization. Cpd43 exerted significant anti-inflammatory effects on a severe experimental model of RA, in which endogenous AnxA1, the natural ligand for FPR2, also exerted inhibitory effects. In addition, Cpd43 reduced RANKL-mediated osteoclastogenesis and inhibited the production of IL-6 by macrophages, as well the activation of human RA FLS, through effects that appeared to be dependent on interaction with FPR2. These findings suggest that therapeutic agonists of FPR may have important beneficial actions on inflammation and bone loss in RA.