Prostaglandin (PG) D2 elicits responses through either the DP1 and/or DP2 receptor. Experimental evidence suggests that stimulation of the DP1 receptor contributes to allergic responses, such that antagonists are considered to be directed
therapies for allergic diseases. In this study, we demonstrate the activity of a novel synthetic DP1 receptor antagonist termed
asapiprant (S-555739) for the DP1 receptor and other receptors in vitro, and assess the efficacy of
asapiprant in several animal models of allergic diseases. We determined the affinity and selectivity of
asapiprant for the DP1 receptor in binding assays. In the animal models of
allergic rhinitis, changes in nasal resistance, nasal secretion, and cell infiltration in nasal mucosa were assessed after
antigen challenge with and without
asapiprant. Similarly, in the animal models of
asthma, the effect of
antigen challenge with and without
asapiprant on
antigen-induced bronchoconstriction,
airway hyper-responsiveness,
mucin production, and cell infiltration in lung were assessed. In binding studies,
asapiprant exhibited high affinity and selectivity for the DP1 receptor. Significant suppression of
antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed with
asapiprant treatment. In addition, treatment with
asapiprant suppressed
antigen-induced asthmatic responses,
airway hyper-responsiveness, and cell infiltration and
mucin production in lung. These results show that
asapiprant is a potent and selective DP1 receptor antagonist, and exerts suppressive effects in the animal models of allergic diseases. Thus,
asapiprant has potential as a novel
therapy for allergic airway diseases.