OC000459 is a potent, selective DP2 antagonist that displaces [3H]prostaglandin D2 ([3H]PGD2) from human recombinant DP2 receptors (Ki = 13 nM), rat recombinant DP2 receptors (Ki = 3 nM), and human native DP2 (Ki = 4 nM; Th2 cell membranes) without interfering with the ligand binding properties of other prostanoid receptors, including PGE1–4, DP1, TP, PGI2, and PGF. OC000459 inhibits chemotaxis and cytokine production of human Th2 lymphocytes with IC50 values of 28 and 19 nM, respectively, and competitively antagonizes eosinophil shape change responses induced by PGD2 in both isolated human leukocytes (pKB = 7.9) and human whole blood (pKB = 7.5). OC000459 was shown to inhibit blood eosinophilia in rats induced by 13,14-dihydro-15-keto PGD2 (ED50 = 0.04 mg/kg) and airway eosinophilia in guinea pigs in response to an aerosol of 13,14-dihydro-15-keto PGD2 (ED50 = 0.01 mg/kg).
