| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Zoniporide targets the sodium-hydrogen exchanger isoform 1 (NHE-1, SLC9A1), a membrane transporter that exchanges extracellular Na+ for intracellular H+. During ischemia-reperfusion, NHE-1 is activated, leading to intracellular Na+ overload and subsequent Ca2+ overload via the Na+/Ca2+ exchanger (NCX), which contributes to myocardial injury. NHE-1 inhibition reduces Ca2+ overload, limiting cell death and preserving cardiac function.
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| ln Vitro |
In vitro, Zoniporide is a potent and selective NHE-1 inhibitor. It inhibits 22Na+ uptake by human NHE-1-expressing fibroblasts in a concentration-dependent manner with an IC₅0 of 14 nM. It also inhibits platelet swelling in vitro with an IC₅0 of 0.059 uM. It has high aqueous solubility and acceptable pharmacokinetics for intravenous administration. It demonstrates little activity against NHE-2.
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| ln Vivo |
In vivo, Zoniporide has been studied for cardioprotective effects in animal models. In rodent models of myocardial infarction, intravenous administration of Zoniporide (0.1-1 mg/kg) prior to reperfusion reduces infarct size by 30-50% and improves cardiac function. It also reduces arrhythmias and preserves ATP levels. It has been evaluated in phase 1 clinical trials.
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| Enzyme Assay |
For NHE-1 activity assays (non-cell-based), 22Na+ uptake assays are performed using PS120 fibroblasts stably expressing human NHE-1. Cells are seeded in 24-well plates, acid-loaded (NH4Cl prepulse), and incubated with Zoniporide (0.01-1000 nM) and 22Na+ (1 uCi/mL) for 3-5 min. Uptake is stopped by washing with ice-cold PBS, cells are lysed, and radioactivity is counted. IC₅0 is calculated. For selectivity, similar assays are performed with NHE-2, NHE-3, and NHE-5-expressing cells.
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| Cell Assay |
For in vitro cellular assays, human platelets are isolated from whole blood, loaded with BCECF-AM (a pH-sensitive dye), and treated with Zoniporide (0.1-1000 nM) before acid load. Platelet swelling is measured by light scattering. For cardiomyocytes, neonatal rat ventricular myocytes are subjected to simulated ischemia-reperfusion; Zoniporide (10-100 nM) reduces cell death and Ca2+ overload measured by Fluo-4. For cytotoxicity, cells are treated with 0.1-100 uM Zoniporide for 48 h; IC₅0 > 10 uM.
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| Animal Protocol |
For in vivo efficacy studies in animal models of myocardial ischemia-reperfusion (MI/R), male Sprague-Dawley rats (250-300 g) are anesthetized, and the left anterior descending (LAD) coronary artery is occluded for 30 min, followed by 120 min reperfusion. Zoniporide (0.1-1 mg/kg) is administered intravenously 5 min before reperfusion. Infarct size is measured by TTC staining, and cardiac function is assessed by echocardiography. Plasma troponin I and CK-MB levels are measured. For a phase 1 clinical trial, healthy volunteers (n=10-20) received single and multiple IV doses of Zoniporide to assess safety, tolerability, and PK. Doses ranged from 0.5-30 mg/kg.
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| ADME/Pharmacokinetics |
Zoniporide has high aqueous solubility and acceptable PK for IV administration. In humans, after IV infusion, Tmax is at the end of infusion, t½ is 2-4 hours, and clearance is moderate. Plasma protein binding is approximately 50-70%. It is not orally bioavailable (<10%). Excreted in urine as unchanged drug and metabolites.
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| Toxicity/Toxicokinetics |
Zoniporide is generally well tolerated at therapeutic doses (0.5-30 mg/kg IV). In phase 1 trials, adverse events were mild to moderate (headache, nausea, injection site pain). No significant QTc prolongation. Preclinical toxicity: no genotoxicity; mild hepatotoxicity at high doses (>50 mg/kg). Not for human use without IND.
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| References | |
| Additional Infomation |
Zoniporide is a small molecule drug. The international nonproprietary name stem "-poride" in its name indicates that zoniporide is a sodium/hydrogen ion reverse transport inhibitor. The monoisotope molecular weight of zoniporide is 320.14 Da. It inhibits sodium-hydrogen exchanger isoenzyme-1 (NHE-1).
Zoniporide is a research compound for NHE-1 inhibition and cardioprotection. It is not an FDA-approved drug. Clinical development may have been discontinued. For research use only. |
| Molecular Formula |
C17H16N6O
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|---|---|
| Molecular Weight |
320.35
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| Exact Mass |
320.139
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| CAS # |
241800-98-6
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| PubChem CID |
6433110
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| Appearance |
White to off-white solid powder
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| Density |
1.54g/cm3
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| Boiling Point |
590.3ºC at 760mmHg
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| Flash Point |
310.8ºC
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| Vapour Pressure |
6.53E-14mmHg at 25°C
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| Index of Refraction |
1.795
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| LogP |
3.296
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
515
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N/N=C/NC(C1=C(C2CC2)N(C2C=CC=C3C=2C=CC=N3)N=C1)=O
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| InChi Key |
GDXBRVCQGGKXJY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16N6O/c18-17(19)22-16(24)12-9-21-23(15(12)10-6-7-10)14-5-1-4-13-11(14)3-2-8-20-13/h1-5,8-10H,6-7H2,(H4,18,19,22,24)
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| Chemical Name |
5-cyclopropyl-N-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide
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| Synonyms |
Zonipolid; CP-597396
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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 : ~125 mg/mL (~390.20 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1216 mL | 15.6079 mL | 31.2159 mL | |
| 5 mM | 0.6243 mL | 3.1216 mL | 6.2432 mL | |
| 10 mM | 0.3122 mL | 1.5608 mL | 3.1216 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.
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