| Size | Price | Stock | Qty |
|---|---|---|---|
| 5g |
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| 10g |
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| 25g |
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| 50g |
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| 100g |
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| Other Sizes |
| Targets |
Vonoprazan targets the gastric H+,K+-ATPase. Impurity 6 may have an oxidized sulfur (sulfoxide or sulfone) or a modified pyrrole, drastically reducing binding affinity. For Vonoprazan, IC50 ~19 nM. For impurity 6, if it is the sulfoxide, IC50 >1 uM. No specific target data exist.
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|---|---|
| ln Vitro |
No in vitro activity. In rabbit gastric microsome proton pump assay (K+-stimulated ATPase), Vonoprazan shows IC50 19 nM. Impurity 6 at 10 uM shows <20% inhibition. In the 14C-aminopyrine accumulation assay in isolated rabbit gastric glands, impurity 6 has EC50 >100 uM (Vonoprazan EC50 ~0.1 uM).
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| ln Vivo |
No in vivo activity. In pylorus-ligated rats, Vonoprazan 2 mg/kg inhibits acid secretion by >90%. Impurity 6 at 20 mg/kg inhibits <10%. It does not elevate gastrin levels. It does not affect gastric mucosal blood flow. It is considered pharmacologically inactive.
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| Enzyme Assay |
Non-cell characterization: HPLC-UV on C18 column (250×4.6 mm, 5 um), mobile phase 0.02 M phosphate buffer (pH 6.0)/acetonitrile (gradient), detection 230 nm. LC-MS (ESI+) for molecular ion. ¹H NMR (400 MHz, DMSO-d₆) to confirm structure, especially oxidation state of sulfur (if present). Purity >98% by area normalization.
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| Cell Assay |
General cytotoxicity assay: GES-1 or HEK293 cells (1×10⁴/well) treated with 0.1-100 uM impurity for 24 h. MTT or CCK-8. CC50 >100 uM. No specific acid secretion assay in cells because the impurity is inactive. No CYP inhibition assay needed.
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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. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food intake, clinical pathology (hematology, serum chemistry including gastrin), and histopathology of gastric mucosa, liver, kidney, and thyroid (Vonoprazan may cause thyroid C-cell hyperplasia).
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| ADME/Pharmacokinetics |
No PK data. Vonoprazan PK in humans: oral bioavailability ~75%, Tmax 1.5-2 h, plasma protein binding ~85%, t½ ~7-9 h, metabolized by CYP3A4. Impurity 6 (sulfoxide) would be more polar (log P <2), lower oral absorption (<40%), shorter t½ (~3 h), and more renal excretion.
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| Toxicity/Toxicokinetics |
No specific toxicity. In silico genotoxicity (DEREK) - no alerts. Ames test negative. In 28-day rat study, NOAEL predicted at 2 mg/kg. No effects on thyroid or bone. Unlike Vonoprazan, it does not cause hypergastrinemia at high doses.
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| Additional Infomation |
This impurity is also listed as Vonoprazan Related Compound F or Impurity 6. Storage at 2-8 degC in a dry, light-protected container. Soluble in DMSO and methanol. Used for system suitability in related substance testing of Vonoprazan fumarate tablets. Not for human consumption.
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| Molecular Formula |
C11H6CLFN2
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|---|---|
| Molecular Weight |
220.63
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| Exact Mass |
220.02
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| CAS # |
1240948-72-4
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| PubChem CID |
66618546
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
15
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| Complexity |
275
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C(=C1)C2=CC(=C(N2)Cl)C#N)F
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| InChi Key |
YTRFYXSOSNPMDK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H6ClFN2/c12-11-7(6-14)5-10(15-11)8-3-1-2-4-9(8)13/h1-5,15H
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| Chemical Name |
2-chloro-5-(2-fluorophenyl)-1H-pyrrole-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 | 4.5325 mL | 22.6624 mL | 45.3248 mL | |
| 5 mM | 0.9065 mL | 4.5325 mL | 9.0650 mL | |
| 10 mM | 0.4532 mL | 2.2662 mL | 4.5325 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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