Camlipixant (BLU-5937) is a specific, noncompetitive and orally bioactive P2X3 homotrimer receptor antagonist (inhibitor) with IC50 of 25 nM for hP2X3 homotrimer. Camlipixant showed strong antitussive effects without taste changes. Camlipixant is indicated for the investigational treatment of unexplained, refractory chronic cough.

Physicochemical Properties

Molecular Formula	C23H24F2N4O4
Molecular Weight	458.457872390747
Exact Mass	458.18
Elemental Analysis	C, 60.26; H, 5.28; F, 8.29; N, 12.22; O, 13.96
CAS #	1621164-74-6
PubChem CID	76955630
Appearance	White to off-white solid powder
LogP	3.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	704
Defined Atom Stereocenter Count	1
SMILES	FC1C=C(C(NC)=O)C=C(C=1C1=C(C[C@H]2CN(C(=O)OC)CCO2)N2C=CC(C)=CC2=N1)F
InChi Key	SEHLMRJSQFAPCJ-HNNXBMFYSA-N
InChi Code	InChI=1S/C23H24F2N4O4/c1-13-4-5-29-18(11-15-12-28(6-7-33-15)23(31)32-3)21(27-19(29)8-13)20-16(24)9-14(10-17(20)25)22(30)26-2/h4-5,8-10,15H,6-7,11-12H2,1-3H3,(H,26,30)/t15-/m0/s1
Chemical Name	methyl (2S)-2-[[2-[2,6-difluoro-4-(methylcarbamoyl)phenyl]-7-methylimidazo[1,2-a]pyridin-3-yl]methyl]morpholine-4-carboxylate
Synonyms	Camlipixant; BLU-5937; BLU 5937; BLU5937;
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	IC50: 25 nM (hP2X3), >24000 nM (hP2X2/3), 92 nM (rP2X3), 1820 nM (rP2X2/3), 126 nM (gpP2X3), 3450 nM (gpP2X2/3)[1]
ln Vitro	BLU-5937, or camlipixant, at 500 nM, inhibits ATP-mediated DRG neuron sensitization [1].
ln Vivo	In guinea pigs, the histamine- and ATP-induced allergic cough is lessened by camlipixant (BLU-5937; 3–30 mg/kg; oral)[1]. When compared to control animals, camlipixant (BLU-5937; 10–20 mg/kg; ip) does not change taste perception[1]. Excellent drug-like characteristics of camlipixant (BLU-5937) include outstanding oral bioavailability, low expected human clearance, no penetration of the blood-brain barrier, and a great safety profile[1].
Animal Protocol	Animal/Disease Models: Male Dunkin Hartley guinea pigs[1] Doses: 0.3, 3, 30 mg/kg Route of Administration: PO, approximately 2 h prior to tussive agent exposure Experimental Results: Dramatically decreased the histamine-induced enhancement in the number of citric acid-induced coughs. decreased Dramatically and dose-dependently the ATP-induced enhancement of citric acid-induced coughs.
References	[1]. Garceau D, Chauret N. 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 (218.12 mM) DMSO: 100 mg/mL (218.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 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 (5.45 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 (5.45 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	2.1812 mL	10.9061 mL	21.8122 mL
	5 mM	0.4362 mL	2.1812 mL	4.3624 mL
	10 mM	0.2181 mL	1.0906 mL	2.1812 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.