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50mg |
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250mg |
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500mg |
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Purity: ≥98%
Pantoprazole (BY1023; SKF96022; BY-1023; SKF-96022; Protonix), an approved anti-ulcer drug, is a proton pump inhibitor (PPI) used for short-term treatment of erosion and ulceration of the esophagus caused by GERD (gastroesophageal reflux disease). Pantoprazole acts by inhibiting the activity of H+/K+-ATPase proton pumb in the parietal cells of gastric mucosa. This inhibition affects the acid secretion and thus, pantoprazole are used as drugs for the treatment of various acid-related disorders. Pantoprazole is activated slowly. The activated sulfonamide of pantoprazole binds to Cys813 and Cys822 of the pumb and inhibits acid secretion selectively.
Targets |
Proton pump; H+/K+-ATPase
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ln Vitro |
In EMT-6 and MCF7 cells, pantoprazole (BY1023; 1–10,000 μM) causes concentration-dependent increases in endosomal pH[1]. BY10232, Pantoprazole, can prevent the release of exosomes. Pantoprazole (BY10232) reduces the ability of tumor cells (melanomas, adenocarcinomas, and lymphoma cell lines) to acidify the extracellular medium by blocking V-H+-ATPase activity[2].
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ln Vivo |
When coupled with doxorubicin, pantoprazole (BY1023; 200 mg/kg; IP; once a week for three weeks) dramatically prolongs the tumor development delay of MCF-7 xenografts[1]. In rats with pylorus ligation, pantoprazole (0.3–3 mg/kg, po) dose-dependently reduces basal acid secretion, while in rats with acute fistula, mepirizole-stimulated acid secretion is reduced[4].
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Enzyme Assay |
The action of the H+/K(+)-ATPase inhibitors pantoprazole and omeprazole was compared in different in vitro test systems. In gastric membrane vesicles under conditions shown to result in acidification of the vesicle interior, pantoprazole and omeprazole inhibited H+/K(+)-ATPase activity with IC50 values of 6.8 and 2.4 microM, respectively. When intravesicular acidification was reduced by inclusion of imidazole (5 mM), a membrane permeable weak base, the inhibitory action of omeprazole was partially lost (IC50 30 microM) and that of pantoprazole almost completely lost. After incubation for 40 min with pumping membrane vesicles, a half-maximal reduction in intravesicular H+ concentration occurred at pantoprazole and omeprazole concentrations of 1.1 and 0.6 microM, respectively. Again, when the intravesicular H+ concentration was reduced by inclusion of imidazole (2.5 mM), pantoprazole (20 and 60 microM) did not reduce the remaining intravesicular proton concentration, whereas omeprazole (10 and 30 microM) did. Both drugs inhibited, with similar potency, papain activity at pH 3.0 and inactivated the enzyme in a similar time-dependent manner; at pH 5.0 omeprazole (IC50 17 microM) was more potent than pantoprazole (IC50 37 microM) and enzyme inhibition was faster than with pantoprazole. These results indicate that pantoprazole is a potent inhibitor of H+/K(+)-ATPase under highly acidic conditions and that it is more stable than omeprazole at a slightly acidic pH such as pH 5.0[3].
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Cell Assay |
Murine EMT-6 and human MCF-7 cells were treated with pantoprazole to evaluate changes in endosomal pH using fluorescence spectroscopy, and uptake of doxorubicin using flow cytometry. Effects of pantoprazole on tissue penetration of doxorubicin were evaluated in multilayered cell cultures (MCC). Pantoprazole (>200 μmol/L) increased endosomal pH in cells, and also increased nuclear uptake of doxorubicin. Pretreatment with pantoprazole increased tissue penetration of doxorubicin in MCCs [1].
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Animal Protocol |
Animal/Disease Models: Mice bearing MCF-7 or A431 xenografts[1]
Doses: 200 mg/kg Route of Administration: IP; once a week for 3 weeks; alone or 2 hrs (hours) before Doxorubicin (6 mg/kg iv) Experimental Results: demonstrated even greater growth delay of MCF-7 xenografts with Doxorubicin compared with the single-dose combination. Dramatically increased tumor growth delay with a single dose with Doxorubicin. There is no effect on growth delay alone. |
References |
[1]. Krupa J Patel, et al. Use of the proton pump inhibitor pantoprazole to modify the distribution and activity of doxorubicin: a potential strategy to improve the therapy of solid tumors. Clin Cancer Res. 2013 Dec 15;19(24):6766-76.
[2]. Huarui Zhang, et al. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330. [3]. W Beil, et al. Pantoprazole: a novel H+/K(+)-ATPase inhibitor with an improved pH stability. Eur J Pharmacol. 1992 Aug 6;218(2-3):265-71. [4]. K Takeuchi, et al. Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole. J Gastroenterol Hepatol. 1999 Mar;14(3):251-7. |
Additional Infomation |
Pantoprazole is a member of the class of benzimidazoles that is 1H-benzimidazole substituted by a difluoromethoxy group at position 5 and a [(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl group at position 2. It has a role as an anti-ulcer drug, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, a xenobiotic and an environmental contaminant. It is a member of benzimidazoles, a member of pyridines, an aromatic ether, an organofluorine compound and a sulfoxide. It is a conjugate acid of a pantoprazole(1-).
Pantoprazole is a first-generation proton pump inhibitor (PPI) used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of H. pylori infections along with other antibiotics including [amoxicillin], [clarithromycin], and [metronidazole], for example. Its efficacy is considered similar to other medications within the PPI class including [omeprazole], [esomeprazole], [lansoprazole], [dexlansoprazole], and [rabeprazole]. Pantoprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of pantoprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, pantoprazole's duration of antisecretory effect persists longer than 24 hours. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life. PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. Pantoprazole doses should be slowly lowered, or tapered, before discontinuing as rapid discontinuation of PPIs such as pantoprazole may cause a rebound effect and a short term increase in hypersecretion. Pantoprazole is a Proton Pump Inhibitor. The mechanism of action of pantoprazole is as a Proton Pump Inhibitor. |
Molecular Formula |
C16H15F2N3O4S
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Molecular Weight |
383.37
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Exact Mass |
383.07513
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Elemental Analysis |
C, 50.13; H, 3.94; F, 9.91; N, 10.96; O, 16.69; S, 8.36
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CAS # |
102625-70-7
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Related CAS # |
Pantoprazole sodium;138786-67-1;Pantoprazole sodium hydrate;164579-32-2;S-Pantoprazole sodium trihydrate;1416988-58-3;Pantoprazole-d6;922727-65-9;Pantoprazole-d3;922727-37-5
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PubChem CID |
4679
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Appearance |
Typically exists as off-white to light yellow solids at room temperature
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Density |
1.5±0.1 g/cm3
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Boiling Point |
586.9±60.0 °C at 760 mmHg
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Melting Point |
139-140ºC
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Flash Point |
308.7±32.9 °C
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Vapour Pressure |
0.0±1.6 mmHg at 25°C
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Index of Refraction |
1.643
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LogP |
1.69
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tPSA |
105.54
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SMILES |
O=S(C1=NC2=CC=C(OC(F)F)C=C2N1)CC3=NC=CC(OC)=C3OC
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InChi Key |
IQPSEEYGBUAQFF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C16H15F2N3O4S/c1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16/h3-7,15H,8H2,1-2H3,(H,20,21)
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Chemical Name |
1H-Benzimidazole, 5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6084 mL | 13.0422 mL | 26.0845 mL | |
5 mM | 0.5217 mL | 2.6084 mL | 5.2169 mL | |
10 mM | 0.2608 mL | 1.3042 mL | 2.6084 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.