OC000459 (Timapiprant) is a potent, selective, and orally active D prostanoid receptor 2 (DP2, CRTH2) antagonist with Ki of 13/3 nM for human/recombinant DP2, respectively.
OC000459 does not interfere with the ligand binding properties or functional activities of other prostanoid receptors (prostaglandin E1-4 receptors, D1, thromboxane receptor, prostacyclin receptor, and prostaglandin F receptor).
OC000459 inhibited chemotaxis (IC50= 28 nM) of human Th2 lymphocytes and cytokine production (IC50=19 nM) by human Th2 lymphocytes.
OC000459 competitively antagonized eosinophil shape change responses induced by PGD₂ in both isolated human leukocytes (pK(B)=7.9) and human whole blood (pK(B)=7.5) but did not inhibit responses to eotaxin, 5-oxo-eicosatetraenoic acid, or complement component C5a.
OC000459 is orally bioavailable in rats and effective in inhibiting blood eosinophilia induced by 13,14-dihydro-15-keto-PGD₂ (DK-PGD₂) with ED50 of 0.04 mg/kg (p.o.) and airway eosinophilia in response to an aerosol of DK-PGD₂ in guinea pigs (ED50=0.01 mg/kg p.o.).