(E/Z)-Sivopixant ((E/Z)-S-600918) is a potent P2X3 receptor antagonist (inhibitor) with IC50 of 4 nM. (E/Z)-Sivopixant may be used in respiratory disease study.

Physicochemical Properties

Molecular Formula	C25H22CLN5O5
Molecular Weight	507.93
Exact Mass	507.13
CAS #	1640808-39-4
Related CAS #	Sivopixant;2414285-40-6
PubChem CID	117752163
Appearance	White to off-white solid powder
LogP	3.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	9
Heavy Atom Count	36
Complexity	826
Defined Atom Stereocenter Count	1
SMILES	ClC1C=CC(=CC=1)CN1C(NC2=CC=C(C=C2)OC2=CC=CC=N2)=NC(=O)N(C[C@@H](C(O)=O)C)C1=O
InChi Key	SKZQFKBIJUXXCG-INIZCTEOSA-N
InChi Code	InChI=1S/C25H22ClN5O5/c1-16(22(32)33)14-31-24(34)29-23(30(25(31)35)15-17-5-7-18(26)8-6-17)28-19-9-11-20(12-10-19)36-21-4-2-3-13-27-21/h2-13,16H,14-15H2,1H3,(H,32,33)(H,28,29,34)/t16-/m0/s1
Chemical Name	(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridin-2-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic 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

Targets	IC50: 4 nM (P2X3 receptor)[1]
ln Vitro	ATP receptors can be broadly categorized into two families: the G protein coupled type P2Y family and the ion channel type P2X family. Within the P2X receptor family, seven subtypes have been identified. These subtypes work as non-selective cation channels by joining forces to create homotrimers or heterotrimers with other P2X subtypes. Moreover, P2X3 receptors are found in the lungs' neuroepithelial bodies (NEB), which is responsible for coughing triggered by ATP. It has been proposed that it plays a role in the respiratory organs' information transmission[1].
References	[1]. Amino-triazine derivatives and pharmaceutical composition containing said derivatives. WO2014200078A1.
Additional Infomation	Drug Indication Treatment of unexplained or refractory chronic cough

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (196.88 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.92 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 (4.92 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 (4.92 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	1.9688 mL	9.8439 mL	19.6878 mL
	5 mM	0.3938 mL	1.9688 mL	3.9376 mL
	10 mM	0.1969 mL	0.9844 mL	1.9688 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.