OC000459 is a potent, selective and orally active antagonist of D prostanoid receptor 2 (DP2) with Ki value of 4nM [1].
DP2 is expressed on Th2 cells and eosinophils. It is activated by PGD2 which is reported to have effects on the pathogenesis of allergic disease. As an antagonist of DP2, OC000459 can prevent PGD2 from binding to human DP2 and rat recombinant DP2 with Ki values of 4nM and 3nM. In CHO cells expressing DP2, OC000459 suppresses PGD2 mediated calcium mobilization with IC50 value of 28nM. In human Th2 cells, OC000459 inhibits chemotaxis and production of IL-13 in response to PGD2 with IC50 values of 28nM and 19nM. In addition, oral administration of OC000459 effectively reduces blood eosinophilia in rats. OC000459 also shows inhibitory effect on the accumulation of eosinophil in guinea pigs aerosolized by DK-PGD2. Furthermore, OC000459 is also reported to inhibit the late-phase allergic response in patients with asthma [1, 2].
References:
[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 eosinophils. Journal of Pharmacology and Experimental Therapeutics, 2012, 340(2): 473-482.
[2] Singh D, Cadden P, Hunter M, et al. Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459. European Respiratory Journal, 2013, 41(1): 46-52.