P2X3 antagonist 34 is a potent, selective, orally bioactive P2X3 homotrimeric receptor blocker (antagonist) with IC50s of 25 nM, 92 nM and 126 nM for human P2X3, rat P2X3 and guinea pig P2X3 receptors, respectively. . P2X3 antagonist 34 is less active against human, rat and guinea pig P2X2/3 heterotrimeric receptors. P2X3 antagonist 34 has strong anti-tussive effects.

Physicochemical Properties

Molecular Formula	C24H26F2N4O3
Molecular Weight	456.4851
Exact Mass	456.197
CAS #	2417288-67-4
PubChem CID	132129813
Appearance	Off-white to light yellow solid powder
LogP	4.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	701
Defined Atom Stereocenter Count	1
SMILES	FC1C([H])=C(C(N([H])C([H])([H])[H])=O)C([H])=C(C=1C1=C(C([H])([H])[C@@]2([H])C([H])([H])N(C(=O)OC([H])([H])[H])C([H])([H])C([H])([H])C2([H])[H])N2C([H])=C([H])C(C([H])([H])[H])=C([H])C2=N1)F
InChi Key	HHJIZLMOCIYWJF-HNNXBMFYSA-N
InChi Code	InChI=1S/C24H26F2N4O3/c1-14-6-8-30-19(10-15-5-4-7-29(13-15)24(32)33-3)22(28-20(30)9-14)21-17(25)11-16(12-18(21)26)23(31)27-2/h6,8-9,11-12,15H,4-5,7,10,13H2,1-3H3,(H,27,31)/t15-/m0/s1
Chemical Name	methyl (3S)-3-[[2-[2,6-difluoro-4-(methylcarbamoyl)phenyl]-7-methylimidazo[1,2-a]pyridin-3-yl]methyl]piperidine-1-carboxylate
Synonyms	P2X3 antagonist 34; P2X3 antagonist 34
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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 Vitro	P2X3 antagonist 34 (BLU-5937; 500 nM) antagonizes P2X3 homotrimeric receptors to prevent αβ-meATP-induced sensitization of isolated primary nociceptors in the rat dorsal root ganglion (DRG). as well as the discharge process. Following washout, both the sensitizing effect of αβ-meATP and the inhibitory impact of P2X3 antagonist 34 are reversible [1].
ln Vivo	The administration of P2X3 antagonist 34 (BLU-5937; 0.3-0 mg/kg, oral; male Dunkin Hartley guinea pigs) to guinea pigs resulted in a dose-dependent reduction in the number of coughs induced by citric acid, which was caused by histamine. model [1]. It has also been demonstrated that the P2X3 antagonist 34 (BLU-5937; orally administered at 3 and 30 mg/kg) significantly and dose-dependently reduces the ATP-induced potentiation of citric acid-induced cough in guinea pigs [1].
Animal Protocol	Animal/Disease Models: Male Dunkin Hartley guinea pig [1] Doses: 0.3 mg/kg, 3 mg/kg, 30 mg/kg Route of Administration: Oral Experimental Results: Significant reduction in the number of histamine-induced citric acid-induced coughs in a dose-dependent manner Way.
References	[1]. BLU-5937: A selective P2X3 antagonist with potent anti-tussive effect and no taste alteration. Pulm Pharmacol Ther. 2019 Jun;56:56-62.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~219.06 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 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 (5.48 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 (5.48 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	2.1906 mL	10.9531 mL	21.9063 mL
	5 mM	0.4381 mL	2.1906 mL	4.3813 mL
	10 mM	0.2191 mL	1.0953 mL	2.1906 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.