| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Vonoprazan targets the gastric H+,K+-ATPase (proton pump) in a potassium-competitive and reversible manner. The binding site is different from that of proton pump inhibitors. Impurity 1 may have altered sulfonyl or pyrrole groups, resulting in significantly reduced enzyme inhibition (IC50 >1 uM vs. vonoprazan IC50 ~10-20 nM in vitro).
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|---|---|
| ln Vitro |
No specific in vitro activity. Vonoprazan inhibits proton pump activity in rabbit gastric microsomes with IC50 19 nM (K+-dependent ATP hydrolysis). For impurity 1, if the sulfonyl group is missing or modified, activity is likely >1000-fold lower. In gastric gland acid secretion assays (14C-aminopyrine accumulation), the impurity is inactive up to 10 uM.
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| ln Vivo |
No in vivo activity. In pylorus-ligated rats, vonoprazan (2 mg/kg p.o.) inhibits gastric acid secretion by >90%. Impurity 1 at 20 mg/kg shows no significant acid reduction. It does not affect serum gastrin levels. Its presence in drug substance does not alter the pharmacodynamics of Vonoprazan.
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| Enzyme Assay |
Non-cell characterization: HPLC-UV method on a C18 column (250×4.6 mm, 5 um), mobile phase 0.02 M KH2PO4 (pH 6.0)/acetonitrile (70:30 to 30:70 gradient), flow 1 mL/min, detection 230 nm. LC-MS (ESI+) to determine [M+H]+. ¹H NMR (400 MHz, DMSO-d₆) to assign protons compared to the known impurity reference standard.
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| Cell Assay |
General cytotoxicity assay: Human gastric epithelial cell line GES-1 or HEK293 cells (1×10⁴/well) are incubated with impurity at 0.1-100 uM for 24-48 h. Cell viability by MTT or CCK-8. No specific proton pump inhibition assay in cells (e.g., intracellular pH measurement using BCECF-AM) because the impurity is inactive.
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| Animal Protocol |
Animal toxicology study: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 0.5, 2, 10 mg/kg/day for 28 days (ICH Q3B). Control receives 0.5% methylcellulose. Endpoints: body weight, food consumption, hematology, serum chemistry (including gastrin), urinalysis, and histopathology of gastric mucosa, liver, kidney, and thyroid.
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| ADME/Pharmacokinetics |
No PK data. Vonoprazan human PK: oral bioavailability ~75%, Tmax 1.5-2 h, plasma protein binding ~85%, t½ ~7-9 h, metabolized by CYP3A4. Impurity 1 with higher polarity (predicted log P <2) may have lower oral absorption (<30%), shorter t½ (<3 h), and higher renal excretion as unchanged drug.
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| Toxicity/Toxicokinetics |
No specific toxicity. In silico genotoxicity assessment (DEREK, Sarah) may reveal no structural alerts. An Ames test (TA98, TA100, TA1535, TA1537, WP2uvrA) with S9 is negative. In a 28-day rat study, NOAEL is expected at 2 mg/kg. No skin sensitization or phototoxicity reported.
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| Additional Infomation |
This impurity is also known as Vonoprazan Related Compound A or Impurity A. Storage at 2-8 degC in a tightly closed container, protected from light. Soluble in DMSO (≥5 mg/mL) and acetonitrile. It is a critical marker for stability-indicating assay methods for Vonoprazan fumarate tablets.
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| Molecular Formula |
C16H10FN3O2S
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|---|---|
| Molecular Weight |
327.34
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| Exact Mass |
327.048
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| CAS # |
1807642-39-2
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| PubChem CID |
141403376
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
568
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C(=C1)C2=CC(=CN2S(=O)(=O)C3=CN=CC=C3)C#N)F
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| InChi Key |
PZUUKJCBWCBPQJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H10FN3O2S/c17-15-6-2-1-5-14(15)16-8-12(9-18)11-20(16)23(21,22)13-4-3-7-19-10-13/h1-8,10-11H
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| Chemical Name |
5-(2-fluorophenyl)-1-pyridin-3-ylsulfonylpyrrole-3-carbonitrile
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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 | 3.0549 mL | 15.2746 mL | 30.5493 mL | |
| 5 mM | 0.6110 mL | 3.0549 mL | 6.1099 mL | |
| 10 mM | 0.3055 mL | 1.5275 mL | 3.0549 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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