AMG-009

AMG-009 is a potent antagonist of prostaglandin D2, with IC₅₀ of 3 nM and 12 nM for CRTH2 and DP receptors, respectively. IC50 & Target: IC50: 3 nM (CRTH2), 12 nM (DP)^[3] In Vitro: AMG-009 inhibits PGD2-induced down-modulation of CRTH2 on CD16 negative granulocytes (eosinophils) in human whole blood with a K_i of 1 nM. AMG 009 also inhibits PGD2-induced cAMP response mediated by DP in platelets in 80% human whole blood with a K_i of 148 nM. AMG 009 inhibits guinea pig CRTH2 receptors (IC₅₀=3 nM) and a PGD2-induced cAMP response assay with cells expressing the guinea pig DP receptors (K_i=131 nM)^[1]. In Vivo: AMG 009 (3, 10 or 30 mg/kg, s.c.) results in a dose dependent decrease in airway resistance provoked by PGD2 aerosol in an acute guinea pig model^[1]. In a guinea pig model of PGD2-induced airway constriction, AMG 009 significantly improves DP potency, with K_b of 82 nM^[2].