FPR agonist Compound 17b is a small-molecule FPR1/FPR2 agonist withEC50 of 3.2 uM (hFPR1 Ca2+ mobilization), lack of functional responses at FPR3.
FPR agonist Compound 17b is a biased agonist at FPR2, ∼30-fold biased away from Cai2+ at both FPR1 and FPR2.
FPR agonist Compound 17b stimulated a concentration-dependent phosphorylation of key cardiomyocyte survival pathways ERK1/2, Akt1/2/3(Thr308) and Akt1/2/3(Ser474), and an increase in Cai2+, inhibited forskolin-stimulated cAMP accumulation in hFPR1-CHO and hFPR2-CHO cells, consistent with FPR1/2 coupling to Gi/o proteins and inhibiting adenylate cyclase.
FPR agonist Compound 17b demonstrated protective actions against cardiomyocyte injury responses in vitro.
FPR agonist Cmpd17b reduces cardiac necrosis 24h post I–R injury in vivo, reduces systemic inflammation, and limits cardiac remodelling and dysfunction in vivo.
