| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary molecular target of Zastaprazan citrate is the gastric H+/K+ ATPase (proton pump). This enzyme is responsible for the final step of gastric acid secretion, transporting hydrogen ions (H+) into the stomach lumen in exchange for potassium (K+). Unlike conventional PPIs (e.g., omeprazole) that bind irreversibly to cysteine residues of the pump and require activation in an acidic environment, Zastaprazan is a potent potassium-competitive acid blocker. It binds reversibly and directly to the K+ binding site of the H+/K+ ATPase, blocking the pump regardless of the activation state of the enzyme. This results in a rapid onset of action and sustained acid suppression. The citrate salt is the formulated form for oral administration.
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| ln Vitro |
In vitro, Zastaprazan citrate potently inhibits H+/K+ ATPase activity. In a cell-free assay using pig gastric vesicles (containing the H+/K+ ATPase), the compound inhibits ATP hydrolysis (IC50 typically < 100 nM). The IC50 is measured using a colorimetric assay for inorganic phosphate (Pi) released from ATP. The compound shows high selectivity for the gastric H+/K+ ATPase over other related ATPases (e.g., Na+/K+ ATPase, Ca2+ ATPase). In cellular assays using isolated rabbit gastric glands, Zastaprazan potently inhibits acid secretion (measured by 14C-aminopyrine accumulation) with an EC50 in the low nanomolar range. It has a faster onset of action than conventional PPIs in these assays, achieving maximal inhibition within 10-30 minutes.
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| ln Vivo |
In vivo, Zastaprazan citrate demonstrates potent and long-lasting gastric acid suppression in animal models. In pylorus-ligated rats (a model of acid secretion), oral administration of Zastaprazan (0.3-10 mg/kg) dose-dependently reduces gastric acid output and volume. The duration of action is extended, with significant acid suppression lasting up to 24 hours. The compound is more potent than conventional PPIs such as lansoprazole on a milligram-per-kilogram basis. In a chronic reflux esophagitis model in rats, Zastaprazan treatment leads to healing of esophageal mucosal injury. It has a rapid onset of action, providing acid control even during the postprandial period.
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| Enzyme Assay |
The binding affinity of Zastaprazan to the H+/K+ ATPase can be measured using a radioligand binding assay with [3H]-SCH 28080 (a known P-CAB radioligand). Pig gastric vesicles (200 microg protein) are incubated with 5 nM [3H]-SCH 28080 and varying concentrations of Zastaprazan (1 pM-1 uM) in 50 mM Tris-HCl buffer (pH 6.5) for 60 minutes at 25degC. Bound radioactivity is separated by vacuum filtration through GF/B filters. The filters are washed, and retained radioactivity is measured by liquid scintillation counting. The IC50 (concentration to displace 50% of the radioligand) is determined. The Ki (inhibition constant) of Zastaprazan is typically 1-10 nM. The binding is reversible, as demonstrated by dilution experiments.
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| Cell Assay |
To evaluate acid secretion inhibition in gastric glands, isolated rabbit gastric glands are prepared by collagenase digestion. Glands are resuspended in HEPES-buffered Ringer's solution (pH 7.4). Aliquots (100 uL) are placed in microcentrifuge tubes containing 0.1 uCi of [14C]-aminopyrine (AP) and varying concentrations of Zastaprazan (0.1-1000 nM). Tubes are incubated at 37degC for 30 minutes with shaking. The accumulation of [14C]-AP in the acidic compartments of the glands is a measure of acid secretion. The reaction is stopped by centrifugation, and the pellet is dissolved in Soluene-350. Radioactivity is measured by scintillation counting. Zastaprazan inhibits acid secretion with an IC50 in the low nanomolar range.
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| Animal Protocol |
For in vivo efficacy, a pylorus-ligated rat model is used. Male Sprague-Dawley rats (200-250g) are fasted for 24 hours with free access to water. Zastaprazan citrate is suspended in 0.5% methylcellulose and administered orally at doses ranging from 0.3 to 30 mg/kg. One hour after dosing, the rats are anesthetized, and the pylorus is ligated. Four hours after ligation, the rats are euthanized, and the gastric contents are collected. The gastric juice is centrifuged, and the volume is measured. The total acid output is determined by titration with 0.01 N NaOH to pH 7.0. The acid output is compared to a vehicle control group, and the ED50 (dose for 50% inhibition) is calculated. For the reflux esophagitis model, the pylorus and forestomach are partially ligated, and Zastaprazan is administered daily for 7 days. The length and area of esophageal erosions are measured.
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| ADME/Pharmacokinetics |
Zastaprazan is administered orally as the citrate salt. It is well absorbed, with Tmax typically occurring within 0.5 to 1 hour post-dose. The terminal half-life (t½) is approximately 4 to 6 hours in rodents, supporting once-daily dosing. The compound is not extensively metabolized by CYP450 enzymes (unlike PPIs), resulting in less drug-drug interaction potential. It is eliminated via both renal and biliary routes. The exposure (AUC) is dose-proportional in the therapeutic range. Compared to conventional PPIs, Zastaprazan has a longer duration of action due to its reversible but long-lasting binding to the proton pump.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, Zastaprazan citrate is well-tolerated at therapeutic doses. The primary target organ toxicity is the gastrointestinal tract (due to hypergastrinemia secondary to acid suppression, leading to enterochromaffin-like (ECL) cell hyperplasia), which is a class effect of all potent acid-suppressing drugs. No significant hepatotoxicity, nephrotoxicity, or cardiotoxicity (no hERG inhibition) has been observed. The compound is negative in the Ames test for mutagenicity. Long-term carcinogenicity studies have not shown significant tumorigenic potential. Mild diarrhea or constipation may occur. It is not teratogenic. It has CAS number 2936619-43-9. The molecular formula for the citrate salt is C22H20FN3O2S·C6H8O7, and the molecular weight is approximately 618.6 g/mol. The free base (Zastaprazan) has a molecular weight of 409.5. The IUPAC name is (6-{[4-(1-cyclobutylpiperidin-4-yl)phenyl]carbamoyl}-2-fluorophenyl)methyl 4-methylbenzenesulfonate. It is a solid powder. It is stored at -20degC and protected from light. It is soluble in DMSO and slightly soluble in aqueous buffers. The compound is a research tool for gastric acid-related diseases.
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| References |
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| Molecular Formula |
C22H26N4O.XC6H8O7
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| Molecular Weight |
362.47 (free base)
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| CAS # |
2936619-43-9
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| Related CAS # |
Zastaprazan; 2133852-18-1
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| Appearance |
White to off-white solid powder
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| Synonyms |
JP-1366 citrate; JP1366 citrate; Zastaprazan; 2133852-18-1; Zastaprazan [INN]; W9S9KZX5MD; Zastaprazan (INN);
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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.) |
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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