1. Academic Validation
  2. Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma

Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma

  • Eur J Pharmacol. 2015 Oct 15;765:15-23. doi: 10.1016/j.ejphar.2015.08.003.
Go Takahashi 1 Fujio Asanuma 1 Noriko Suzuki 2 Maki Hattori 3 Shingo Sakamoto 4 Akira Kugimiya 2 Yasuhiko Tomita 1 Goro Kuwajima 5 William M Abraham 6 Masashi Deguchi 7 Akinori Arimura 5 Michitaka Shichijo 8
Affiliations

Affiliations

  • 1 Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
  • 2 Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
  • 3 Research Technology Services, Shionogi Techno Advance Research, Toyonaka, Osaka, Japan.
  • 4 Research Laboratory for Development, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
  • 5 Global Project Management, Shionogi & Co., Ltd., Osaka, Japan.
  • 6 Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
  • 7 Strategic Research Planning Offices, Pharmaceutical Research Division, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
  • 8 Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan. Electronic address: michitaka.shichijou@shionogi.co.jp.
Abstract

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.

Keywords

Allergic rhinitis; Asapiprant; Nasal congestion; Prostaglandin D(2); Synthetic DP(1) receptor antagonist.

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