Timapiprant

OC000459 is a potent, selective DP₂ antagonist that displaces [³H]prostaglandin D₂ ([³H]PGD₂) from human recombinant DP₂ receptors (K_i = 13 nM), rat recombinant DP₂ receptors (K_i = 3 nM), and human native DP₂ (K_i = 4 nM; Th2 cell membranes) without interfering with the ligand binding properties of other prostanoid receptors, including PGE₁–4, DP₁, TP, PGI₂, and PGF.¹ 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).¹ 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).¹

1.Pettipher, R., Vinall, S.L., Xue, L., et al.Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophilsJ. Pharmacol. Exp. Ther.340(2)473-482(2012)