AZD1981 is a powerful and selective antagonist of CRTh2, effectively competing with radio-labelled PGD2 for binding to the human DP2 receptor, exhibiting a high level of potency (pIC50 = 8.4)[1]. Further, in a guinea pig hind limb model, AZD1981 at 10 nM markedly reduced DK-PGD2-driven eosinophil mobilization by about 50%, a suppression that was complete at 100 nM[1]. AZD1981 demonstrated efficient cross-species DP2 receptor binding activity in mice, rats, guinea pigs, rabbits, and dogs. However, mouse, rat, and rabbit cell systems did not exhibit a response to DP2 agonists, whereas guinea pig and dog systems did, with AZD1981 inhibiting DP2-mediated changes in eosinophil shape and migration from bone marrow, particularly noted in guinea pigs[1]. No positive clinical outcomes were observed with the use of AZD1981 at a dosage of 1000 mg twice daily over a four-week period in individuals with moderate to severe COPD, although the drug was generally well-received without raising safety issues[3].
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