The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is a G protein-coupled receptor that has been reported to modulate inflammatory responses in various rodent models of asthma, allergic rhinitis and atopic dermatitis[3]. MK-7246 is a potent and selective CRTH2 antagonist with a Ki of 2.5 ± 0.5 nM[3]. MK-7246 displays a relatively high selectivity for CRTH2 with an affinity 149-fold lower for the DP receptor (Ki, 373 ± 96 nM) and ≥1500-fold lower for the other prostanoid receptors (Ki, 7668 ± 2169 nM for EP2, 3804 ± 1290 nM for TP). MK-7246 is also tested in a panel of 157 enzyme and receptor assays at concentrations up to 100 μM and small but significant activity is detected only on phosphodiesterase 1 (PDE1, IC50 = 33.2 μM) and MAPK3 (ERK1, IC50 = 49.4 μM)[3]. MK-7246 yields ex vivo blockade of CRTH2 on eosinophils in monkeys and sheep, and it significantly blocks antigen-induced late-phase bronchoconstriction and airway hyper-responsiveness in sheep[3]. In a dose-dependent manner, MK-7246 decreased eosinophil influx and Th2 cytokine production following the alternaria alternata challenge[4].
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