| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 4 nM (P2X3 receptor)[1]
The primary target of (E/Z)-Sivopixant is the P2X3 purinergic receptor. It is a potent antagonist with an IC50 of 4 nM. P2X3 receptors are ATP-gated ion channels found on sensory nerve endings, including those in the lungs' neuroepithelial bodies (NEB), where they play a key role in triggering the cough reflex. By selectively antagonizing these receptors, Sivopixant modulates the sensory signals that lead to coughing. |
|---|---|
| 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].
In vitro, (E/Z)-Sivopixant demonstrates high potency as a P2X3 receptor antagonist, with an IC50 of 4 nM. This activity is typically characterized in cell-based assays using cell lines expressing recombinant P2X3 receptors, where the compound's ability to inhibit agonist (ATP)-evoked responses, such as calcium influx, is measured. |
| ln Vivo |
In vivo, Sivopixant has been evaluated in clinical trials for the treatment of refractory or unexplained chronic cough (R/UCC). While a Phase 2 study did not meet its primary endpoint, the compound has shown efficacy in reducing cough frequency and improving health-related quality of life. A key advantage noted for Sivopixant is its ability to reduce cough without causing significant taste disturbance, a common side effect associated with other P2X3 antagonists.
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| Enzyme Assay |
In vitro binding and functional assays for (E/Z)-Sivopixant involve using cell lines that recombinantly express the human P2X3 receptor. The compound's antagonistic activity is assessed by measuring its ability to inhibit ATP-induced calcium influx or ion currents. IC50 values, such as 4 nM, are determined from concentration-response curves.
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| Cell Assay |
In vitro cellular assays for (E/Z)-Sivopixant are performed using cell lines expressing recombinant P2X3 receptors. Cells are pre-incubated with the compound and then stimulated with ATP. The inhibition of the agonist-induced calcium mobilization or other downstream signals is measured to quantify the antagonist activity.
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| Animal Protocol |
In vivo studies for Sivopixant have progressed to human clinical trials. These trials typically involve oral administration of the compound to patients with refractory or unexplained chronic cough. The primary efficacy endpoints include the measurement of cough frequency and health-related quality of life questionnaires. Safety and tolerability are also key assessments.
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| ADME/Pharmacokinetics |
(E/Z)-Sivopixant is a small molecule with a molecular weight of 507.93 g/mol. It has a LogP of 3.8, indicating moderate lipophilicity. The compound is supplied as a white to off-white solid powder. For storage, the powder can be kept at -20°C for up to 3 years or at 4°C for up to 2 years. Solutions can be stored at -80°C for 6 months or at -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Toxicity data for (E/Z)-Sivopixant is primarily derived from clinical trials. In these studies, the compound has been reported to have very few taste disturbance adverse events, which is a notable improvement over other P2X3 antagonists. Comprehensive toxicity profiles would be available in the clinical study reports. As a research compound, it should be handled with standard safety precautions.
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| References | |
| Additional Infomation |
Drug Indication
Treatment of unexplained or refractory chronic cough. (E/Z)-Sivopixant is a potent, selective P2X3 receptor antagonist (IC50 = 4 nM) developed for the treatment of refractory or unexplained chronic cough. Its mechanism of action involves blocking P2X3 receptors on sensory nerve endings in the airways, thereby modulating the cough reflex. Clinical studies have indicated that it can reduce cough frequency with a favorable side-effect profile, particularly regarding taste disturbance. It represents a promising non-opioid therapy for persistent cough management. |
| Molecular Formula |
C25H22CLN5O5
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|---|---|
| Molecular Weight |
507.93
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| Exact Mass |
507.13
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| CAS # |
1640808-39-4
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| Related CAS # |
Sivopixant;2414285-40-6
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| PubChem CID |
117752163
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| Appearance |
White to off-white solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
36
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| Complexity |
826
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| Defined Atom Stereocenter Count |
1
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| 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
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| InChi Key |
SKZQFKBIJUXXCG-INIZCTEOSA-N
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| 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
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (196.88 mM)
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|---|---|
| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT06776432
Conditions:Sleep ApneaLink: https://clinicaltrials.gov/ct2/show/NCT04110054
Conditions:Chronic CoughProducts are for research use only; We do not sell to patients
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