| Size | Price | Stock | Qty |
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| 10mg |
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| 1g | |||
| Other Sizes |
| Targets |
The primary target of Zoniporide HCl is the sodium-hydrogen exchanger isoform-1 (NHE-1). NHE-1 is involved in intracellular pH homeostasis in many mammalian cell types. By blocking the NHE-1-mediated exchange of intracellular protons for extracellular sodium ions, Zoniporide mitigates the detrimental ion dysregulation and calcium overload that characterize ischemia-reperfusion injury. It exhibits high selectivity for NHE-1 over other isoforms.
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| ln Vitro |
In vitro, Zoniporide inhibited 22Na+ uptake in fibroblasts expressing human NHE-1 in a concentration-dependent manner with an IC50 of 14 nM. It was highly selective (157-fold vs. NHE-2 and 15,700-fold vs. NHE-3). The compound inhibits NHE-1-dependent swelling of human platelets ex vivo with an IC50 of 59 nM. The potency and selectivity of Zoniporide were determined via inhibition of 22Na+ uptake by PS-120 fibroblast cell lines overexpressing human NHE-1, -2 or rat NHE-3.
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| ln Vivo |
In rabbits undergoing open thoracotomy anesthesia, zoniporide (0.25–4 mg/kg; intravenously; hourly for 2 hours) results in a dose-dependent decrease in infarct size (ED50=0.45 mg/kg/h) [1]. Zoniporide contains one main active metabolite and demonstrates modest plasma protein binding in monkeys, with a t1/2 of 1.5 hours [1]. AUC0-∞ and t1/2 of 0.07 μg·h/mL and 0.5 hours, respectively, were seen with Zonipoli therapy [2].
In vivo, Zoniporide (0.25–4 mg/kg; intravenously; hourly for 2 hours) results in a dose-dependent decrease in infarct size in rabbits undergoing open thoracotomy anesthesia, with an ED50 of 0.45 mg/kg/h. Zoniporide contains one main active metabolite and demonstrates modest plasma protein binding in monkeys, with a t1/2 of 1.5 hours. AUC0-∞ and t1/2 of 0.07 μg·h/mL and 0.5 hours were seen with Zoniporide therapy in rats. |
| Enzyme Assay |
In vitro enzyme or receptor binding assays for Zoniporide involve measuring NHE-1 activity by monitoring the recovery of intracellular pH (pHi) following an induced acid load. The rate of pH recovery is proportional to NHE-1 activity. Alternatively, the platelet swelling assay is used to measure NHE-1 inhibitory activity. 22Na+ uptake inhibition assays are performed using PS-120 fibroblast cell lines overexpressing human NHE-1, -2 or rat NHE-3.
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| Cell Assay |
In vitro cell-based assays are performed using PS-120 fibroblast cell lines overexpressing human NHE-1, -2 or rat NHE-3. Cells are treated with varying concentrations of Zoniporide, and 22Na+ uptake is measured. The IC50 for inhibition of 22Na+ uptake is determined. Human platelets are used for ex vivo swelling assays to measure NHE-1-dependent swelling inhibition.
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| Animal Protocol |
Animal/Disease Models: Rabbit [1]
Doses: 0.25, 1, 4 mg/kg Route of Administration: once every hour for 2 hrs (hrs (hours)); intravenous (iv) (iv)injection Experimental Results: There was a significant dose-dependent reduction in infarct area in anesthetized rabbits. ED50 is 0.45 mg/kg/h. Animal/Disease Models: Rat [2] Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)injection (pharmacokinetic/PK/PK analysis) Experimental Results: AUC0-∞ and t1/2 were 0.07 μg·h/mL and 0.5 hrs (hrs (hours)) respectively. In vivo animal experiments are conducted using rabbits undergoing open thoracotomy anesthesia. Zoniporide is administered intravenously at doses of 0.25, 1, and 4 mg/kg, hourly for 2 hours. Infarct size is measured to determine the dose-dependent reduction, with an ED50 of 0.45 mg/kg/h. Pharmacokinetic studies are performed in rats and monkeys to determine AUC, t1/2, and plasma protein binding. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of Zoniporide HCl indicate that it has a molecular weight of 393.27 and a molecular formula of C17H16N6O·2HCl. In rats, AUC0-∞ and t1/2 were 0.07 μg·h/mL and 0.5 hours, respectively. In monkeys, Zoniporide demonstrates modest plasma protein binding with a t1/2 of 1.5 hours. The compound has a LogP of 4.716. It is typically stored at room temperature as a solid.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for Zoniporide HCl are characteristic of a research compound. As an NHE-1 inhibitor, its safety profile is an important consideration. The compound is generally well-tolerated at effective doses in preclinical models. Common side effects may include electrolyte imbalances and gastrointestinal disturbances. The compound is for research use only and not for human use.
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| References |
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| Additional Infomation |
Other information: Zoniporide HCl is also known as CP-597396. It represents a novel class of potent NHE-1 inhibitors with the potential to prevent myocardial ischemic injury in a variety of cardiovascular diseases. The compound is widely studied in cardiovascular pharmacology. Its CAS number is 241800-97-5.
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| Molecular Formula |
C17H16N6O.2[HCL]
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|---|---|
| Molecular Weight |
393.27042
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| Exact Mass |
392.091
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| CAS # |
241800-97-5
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| Related CAS # |
Zoniporide hydrochloride hydrate;863406-85-3
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| PubChem CID |
11962997
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.716
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
515
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N=C(N)NC(C=1C=NN(C1C2CC2)C3=CC=CC4=C3C=CC=N4)=O.Cl
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| InChi Key |
JTEXNYIOROVPIR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16N6O.ClH/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);1H
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| Chemical Name |
5-cyclopropyl-N-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide;hydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.5428 mL | 12.7139 mL | 25.4278 mL | |
| 5 mM | 0.5086 mL | 2.5428 mL | 5.0856 mL | |
| 10 mM | 0.2543 mL | 1.2714 mL | 2.5428 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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