| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
ATP-sensitive inwardly-rectifier potassium channel Kir6.2/SUR1 (IKATP) on pancreatic beta cells. Tifenazoxide is a selective SUR1/Kir6.2 KATP channel opener.
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| ln Vitro |
Tiphenazine (NN414), at least 100 times more powerful than diazoxide, hyperpolarizes βTC3 cell membranes and inhibits insulin release in βTC6, isolated rat islets, and human islets [2]. Tiphenazine and diazoxide had EC50 values in patch-clamp experiments of 0.45 and 31 µM, respectively. When applied at a concentration of 100 µM, tiphenazine activates Kir6.2/SUR1 channels, but not Kir6.2/SUR2A or Kir6.2/SUR2, which are expressed in both inside-out and whole-cell Xenopus laevis oocytes. expressed in recordings on big plaques [2]. Tiphenazine (IC50 = 0.15 µM) is a strong inhibitor of glucose-stimulated insulin release from βTC6 cells [1].
In vitro, Tifenazoxide is at least 100 times more potent than diazoxide. It hyperpolarizes βTC3 cell membranes and inhibits insulin release in βTC6 cells, isolated rat islets, and human islets. The EC₅₀ values in patch-clamp experiments are 0.45 µM for Tifenazoxide compared to 31 µM for diazoxide. At a concentration of 100 µM, Tifenazoxide activates Kir6.2/SUR1 channels but not Kir6.2/SUR2A or Kir6.2/SUR2 channels. Tifenazoxide is a potent inhibitor of glucose-stimulated insulin release from βTC6 cells with an IC₅₀ of 0.15 µM. |
| ln Vivo |
For three weeks, male VDF Zucker (fa/fa) rats given thiphenazine (NN414; 1.5 mg/kg; oral; twice daily) have reduced basal hyperglycemia and improved glucose tolerance. , and enhance in vitro insulin secretory response as well as lower hyperinsulinemia during the oral glucose tolerance test (OGTT) [1].
In vivo, Tifenazoxide administered orally at 1.5 mg/kg twice daily for three weeks to male VDF Zucker rats reduces basal hyperglycemia and improves glucose tolerance. It lowers hyperinsulinemia during the oral glucose tolerance test (OGTT) and enhances the in vitro insulin secretory response. Basal blood glucose decreases dramatically, with an average reduction of 0.64 mM after 3 weeks of treatment. |
| Enzyme Assay |
Non-cell binding assays for Tifenazoxide are performed using membrane preparations from cells expressing Kir6.2/SUR1 or other KATP channel subtypes. Radioligand binding studies are conducted using [³H]glibenclamide or [¹²⁵I]iodoglyburide as tracers. Membranes are incubated with the radioligand and varying concentrations of Tifenazoxide (0.001-100 μM). Nonspecific binding is determined with excess unlabeled glibenclamide. After incubation at 25°C for 60-90 minutes, bound and free ligand are separated by filtration, and radioactivity is counted. IC₅₀ and Ki values are calculated from competition curves to assess SUR1 selectivity.
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| Cell Assay |
Cellular assays for Tifenazoxide are performed using βTC6 cells, isolated rat islets, or human islets. Cells are treated with Tifenazoxide at concentrations ranging from 0.001-100 μM. Insulin release is measured by ELISA or RIA. Patch-clamp electrophysiology is used to record KATP channel activity in inside-out and whole-cell configurations. Membrane potential is measured using fluorescent dyes or microelectrodes. EC₅₀ values for channel activation and insulin release inhibition are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Male Vancouver Diabetic Fat (VDF) Zucker rat [1]
Doses: 1.5 mg/kg Route of Administration: po (po (oral gavage)) twice a day; 3 weeks of treatment Experimental Results: Basal blood glucose diminished Dramatically, with an average decrease of 0.64 after 3 weeks of treatment mM. In vivo animal studies are conducted in male Vancouver Diabetic Fatty (VDF) Zucker rats. Tifenazoxide is administered orally at a dose of 1.5 mg/kg twice daily for 3 weeks. Basal blood glucose, glucose tolerance (OGTT), and hyperinsulinemia are assessed. Insulin secretory response is measured in vitro after treatment. The compound's effects on glucose homeostasis and body weight are evaluated. |
| ADME/Pharmacokinetics |
Tifenazoxide has a molecular weight of 291.77 and a molecular formula of C9H10ClN3O2S2. It is also known as NN414. The compound is orally bioactive. It is typically stored as a powder at -20°C. Tifenazoxide is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Tifenazoxide are limited to research use. No significant toxicity has been reported at effective doses in published studies. Standard safety pharmacology studies would be required for therapeutic development. The compound is for research use only.
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| References |
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| Additional Infomation |
Tifenazine is a thiadiazine derivative with hypoglycemic activity. Similar to sulfonylureas, tifenazine binds to the ATP-sensitive inward rectifier potassium channel Kir6.2/SUR1 (IKATP) on the pancreatic β-cell membrane, stimulating insulin release and thus lowering blood glucose levels.
Tifenazoxide (NN414) is a potent, orally bioactive SUR1/Kir6.2 selective KATP channel opener. It has antidiabetic effects and inhibits glucose-stimulated insulin release. Tifenazoxide is a thiadiazine derivative with hypoglycemic activity. It is not approved for clinical use and is available for research purposes only. |
| Molecular Formula |
C9H10CLN3O2S2
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|---|---|
| Molecular Weight |
291.77
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| Exact Mass |
290.99
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| CAS # |
279215-43-9
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| PubChem CID |
135410911
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| Appearance |
White to off-white solid powder
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| Vapour Pressure |
3.22E-08mmHg at 25°C
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| LogP |
3.059
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
469
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KYSFUHHFTIGRJN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H10ClN3O2S2/c1-9(2-3-9)12-8-11-5-4-6(10)16-7(5)17(14,15)13-8/h4H,2-3H2,1H3,(H2,11,12,13)
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| Chemical Name |
6-chloro-N-(1-methylcyclopropyl)-1,1-dioxo-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine
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| Synonyms |
NN-414; NN 414; Tifenazoxide
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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) |
DMSO : ~100 mg/mL (~342.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.57 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 (8.57 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 (8.57 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 | 3.4274 mL | 17.1368 mL | 34.2736 mL | |
| 5 mM | 0.6855 mL | 3.4274 mL | 6.8547 mL | |
| 10 mM | 0.3427 mL | 1.7137 mL | 3.4274 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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