916047-16-0

The biological effects of prostaglandin D₂ (PGD₂) are transduced by at least two 7-transmembrane G protein-coupled receptors, designated DP₁ and CRTH2/DP₂. In humans, CRTH2/DP₂ is expressed on Th2 cells, eosinophils, and basophils where it mediates the chemotactic activity of PGD₂.¹ CAY10595, as a racemic mixture, is a potent CRTH2/DP₂ receptor antagonist that binds to the human receptor with a K_i value of 10 nM.² The R enantiomer of CAY10595 is significantly more potent exhibiting K_i values of 5.3 and 5 nM at the human and murine CRTH2/DP₂ receptor, respectively. The R enantiomer of CAY10595 inhibits eosinophil chemotaxis induced by 13,14-dihydro-15-keto-PGD₂ with an IC₅₀ value of 7.3 nM.²

1. Hirai, H., Tanaka, K., Yoshie, O., et al. Prostaglandin D₂ selectivity induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2 J. Exp. Med. 193(2),255-261(2001).
2. Crosignani, S., Page, P., Missotten, M., et al. Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP₂) receptor antagonists for the treatment of allergic inflammatory diseases J. Med. Chem. 51,2227-2243(2008).