Fevipiprant (formerly known as NVP-QAW039 or QAW039) is a novel, selective, potent, oral active and reversible competitive CRTh2 (chemoattractant receptor-homologous molecules expressed on T-helper type 2) antagonist with an in vitro dissociation constant KD value of 1.1nM at the CRTh2 receptor and an IC50 value of 0.44 nM for inhibition of PGD2-induced eosinophil shape change in human whole blood. It is currently being developed to treat allergic diseases and may be used to treat asthma. The human CRTh2 receptor (1.14 ± 0.44 nM) expressed in Chinese hamster ovary cells was highly affinified for [(3)H]-QAW039, and the binding was both competitive and reversible with the native agonist prostaglandin D2 (PGD2).

Physicochemical Properties

Molecular Formula	C19H17F3N2O4S
Molecular Weight	426.41
Exact Mass	426.086
Elemental Analysis	C, 53.52; H, 4.02; F, 13.37; N, 6.57; O, 15.01; S, 7.52
CAS #	872365-14-5
Related CAS #	872365-14-5
PubChem CID	23582412
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	637.6±55.0 °C at 760 mmHg
Flash Point	339.4±31.5 °C
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.597
LogP	2.85
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	709
Defined Atom Stereocenter Count	0
SMILES	O=C(CC1=C(C)N(CC2C(C(F)(F)F)=CC(S(C)(=O)=O)=CC=2)C2C1=CC=CN=2)O
InChi Key	GFPPXZDRVCSVNR-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H17F3N2O4S/c1-11-15(9-17(25)26)14-4-3-7-23-18(14)24(11)10-12-5-6-13(29(2,27)28)8-16(12)19(20,21)22/h3-8H,9-10H2,1-2H3,(H,25,26)
Chemical Name	2-[2-methyl-1-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-b]pyridin-3-yl]acetic acid
Synonyms	Fevipiprant; NVP-QAW-039 QAW-039; QAW039; QAW 039; NVP-QAW039; NVP-QAW 039
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

Targets	DP2 ( Kd = 1.14 nM )
ln Vitro	Fevipiprant (0-10 µM) inhibits the expression of the following genes in human Th2 cells stimulated by activated mast cell supernatants: IL-4, IL-3, IL-5, IL-8, CSF1, and CSF2[1].
ln Vivo	Fevipiprant (10 mg/kg; in the drinking water) inhibits the formation of mouse abdominal aortic aneurysms (AAAs) induced by CaCl2[3].
Animal Protocol	C57Bl/6 mice 10 mg/kg In the drinking water
References	[1]. The pharmacology of the prostaglandin D2 receptor 2 (DP2) receptor antagonist, fevipiprant. Pulm Pharmacol Ther. 2021 Jun;68:102030. [2]. Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma. Korean J Intern Med. 2020 May;35(3):619-629. [3]. Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation. Clin Sci (Lond). 2022 Mar 18;136(5):309-321.
Additional Infomation	Fevipiprant has been used in trials studying the treatment of Asthma, Atopic Dermatitis, and Allergic Rhinitis. Drug Indication Treatment of asthma

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 30 mg/mL Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 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 25.0 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: ≥ 2.5 mg/mL (5.86 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 25.0 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: ≥ 2.5 mg/mL (5.86 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 25.0 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	2.3452 mL	11.7258 mL	23.4516 mL
	5 mM	0.4690 mL	2.3452 mL	4.6903 mL
	10 mM	0.2345 mL	1.1726 mL	2.3452 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.