LAS191859

LAS191859 is a potent antagonist of CRTH2/DP2 with IC50 values of 9.58, 14, 15.5, and 7.6 nM for recombinant human, rat, mouse, and guinea pig CRTH2/DP2 receptors, respectively. It is selective for CRTH2/DP2 over a panel of 65 enzymes, ion channels, and transporters with <25% inhibition for all targets when tested at a concentration of 10 μM. LAS191859 reduces shape change of eosinophils (IC50s = 2 and 8.2 nM in isolated eosinophils and whole blood, respectively) and eosinophil chemotaxis (IC50 = 1.3 nM) induced by prostaglandin D2 binding to CRTH2/DP2. Oral administration of LAS191859 reduces PGD2-induced systemic eosinophilia in guinea pigs (ID50 = 131 μg/kg).