Asapiprant (S555739) is a novel, potent and selective Prostaglandin D2receptor 1 (DP1) receptor antagonist (Ki = 0.44 nM) with the potential for treating allergic airway diseases. Asapiprant showed high affinity and selectivity for the DP1 receptor over other targets. After asapiprant treatment, a significant suppression of antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed. Further, 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.

Physicochemical Properties

Molecular Formula	C24H27N3O7S
Molecular Weight	501.5521
Exact Mass	501.157
CAS #	932372-01-5
Related CAS #	932372-01-5
PubChem CID	59232326
Appearance	White to off-white solid powder
LogP	4.186
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	9
Heavy Atom Count	35
Complexity	789
Defined Atom Stereocenter Count	0
InChi Key	ZMZNWNTZRWXTJU-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H27N3O7S/c1-17(2)34-19-4-6-20(7-5-19)35(30,31)27-12-10-26(11-13-27)18-3-8-21(24-25-9-14-32-24)22(15-18)33-16-23(28)29/h3-9,14-15,17H,10-13,16H2,1-2H3,(H,28,29)
Chemical Name	2-[2-(1,3-oxazol-2-yl)-5-[4-(4-propan-2-yloxyphenyl)sulfonylpiperazin-1-yl]phenoxy]acetic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo

Oral treatment of 1 mg/kg and 3 mg/kg of asapilan to sheep significantly (P<0.01) decreased the increase in nasal resistance by 82% and 92%, respectively. Oral injection of 5 mg/kg Asapiprant to sheep decreased prostaglandin (PG) D2 (PGD)2-induced nasal resistance by 86%. Asapiprant (3, 10 and 30 mg/kg) suppressed immediate airway responses (IAR) by 52%, 57% and 96% and late airway responses (LAR) when taken orally 1 hour before antigen challenge to pigs ) are 67%, 50% and 79% respectively. Asapiprant (5 mg/kg) was taken orally for 4 days. Asapiprant significantly (P<0.01) decreased sheep antigen-induced nasal resistance by 73%. Treatment of pigs with 3 and 30 mg/kg Asapiprant significantly (P<0.01) decreased nasal secretions by 53% and 72%, respectively. Treatment of rats with 10 mg/kg Asapiprant significantly reduced airway hyperresponsiveness (AHR), inflammatory cell infiltration, and mucus formation in bronchoalveolar lavage fluid (BALF) despite treatment with 0.1 mg/kg Asapiprant. (P<0.05) had no significant effect on any response [1].

References

[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~11.11 mg/mL (~22.15 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.11 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.11 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.11 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9938 mL	9.9691 mL	19.9382 mL
	5 mM	0.3988 mL	1.9938 mL	3.9876 mL
	10 mM	0.1994 mL	0.9969 mL	1.9938 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.