OC000459

OC000459 is a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils. OC000459 inhibited chemotaxis (IC50 = 0.028 μM) of human Th2 lymphocytes and cytokine production (IC50 = 0.019 μM) by human Th2 lymphocytes. OC000459 also inhibited the activation of Th2 cells and eosinophils in response to supernatants from IgE/anti-IgE-activated human mast cells. OC000459 was shown to inhibit blood eosinophilia in rats induced by 13,14-dihydro-15-keto PGD2 (Item No. 12610) (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). OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis.