Vonoprazan Fumarate (TAK-438)

製品コードS8016 バッチS801602

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

 

C17H16FN3O2S.C4H4O4
分子量 461.46 CAS No. 1260141-27-2
Solubility (25°C)* 体外 DMSO 92 mg/mL (199.36 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
0.5% methylcellulose
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Vonoprazan Fumarate (TAK-438) is a novel P-CAB (potassium-competitive acid blocker) that reversibly inhibits H+/K+, ATPase with IC50 of 19 nM (pH 6.5), controls gastric acid secretion. Phase 3.
in vitro TAK-438 is a pyrrole derivative with a chemical structure that is completely different from the P-CABs developed to date. TAK-438 inhibits gastric H+, K+-ATPase activity in a concentration-dependent manner. Under neutral conditions (pH 7.5), the inhibitory activity of TAK-438 is almost the same as that under weakly acidic conditions (pH 6.5). TAK-438 does not inhibit Na+, K+-ATPase activity even at concentration 500 times higher than their IC50 values against gastric H+,K+-ATPase activity. TAK-438 inhibits gastric H+, K+-ATPase in a K+-competitive manner with Ki of 3 nM. [2]
in vivo TAK-438 inhibits basal gastric acid secretion in a dose-dependent manner, and the ID50 value is 1.26 mg/kg . Intravenous administration of TAK-438 dose-dependently increases the pH of the gastric perfusate, and the increase in pH is sustained for 5 h after administration. At the 1 mg/kg dose, the pH plateaues 90 min after administration, and the highest pH value reached is 5.9. [2] In addition, TAK-438 shows a potent and longer-lasting inhibitory effect on the histamine-stimulated gastric acid secretion in rats and dogs. TAK-438 shows significant antisecretory activity through high accumulation and slow clearance from the gastric tissue. TAK-438 is unaffected by the gastric secretory state, unlike PPIs. [3]
特徴 Capable of inhibiting H+, K+-ATPase under acidic or neutral conditions.

プロトコル(参考用のみ)

キナーゼアッセイ Proton Potassium Adenosine Triphosphatase (H+, K+-ATPase) Inhibitory Activity Test
A gastric mucosal membrane microsomal fraction is prepared from the stomach of swine. First, the stomach is removed, washed with tap water, and immersed in 3 M brine, and the surface of the mucosal membrane is wiped with a paper towel. The gastric mucosal membrane is detached, chopped, and homogenized in a 0.25 M saccharose solution (pH 6.8) containing 1 mM EDTA and 10 mM tris-hydrochloric acid using polytron. The obtained homogenate is centrifuged at 20000g for 30 min and the supernatant is centrifuged at 100000g for 90 min. The precipitate is suspended in 0.25 M saccharose solution, superimposed on a 0.25 M saccharose solution containing 7.5% Ficoll, and centrifuged at 100000g for 5 h. The fraction containing the interface between the both layers is recovered, and centrifugally washed with 0.25 M saccharose solution. The obtained microsomal fraction is used as a proton, potassium adenosine triphosphatase standard product. To 40 μL of a 50 mM HEPES-Tris buffer (5 mM magnesium chloride, 10 mM potassium chloride, 10 μM valinomycin, pH 6.5) containing 2.5 μg/mL (based on the protein concentration) of the enzyme standard product is added a test compound (5 μL) dissolved in a 10% aqueous dimethyl sulfoxide solution, and the mixture is incubated at 37 °C for 30 min. The enzyme reaction is started by adding 5 μL of a 2 mM adenosine triphosphate Tris salt solution (50 mM HEPES-Tris buffer (5 mM magnesium chloride, pH 6.5)). The enzyme reaction is carried out at 37 °C for 20 min, and 15 μL of a malachite green solution (0.12% malachite green solution in sulfuric acid (2.5 mol/L), 7.5% ammonium molybdate, and 11% Tween 20 are mixed at a ratio of 100:25:2) is added to quench the reaction. After the mixture is allowed to stand at room temperature for 15 min, the resulting reaction product of inorganic phosphorus with malachite green is colorimetrically determined at a wavelength of 610 nm. In addition, the amount of the inorganic phosphoric acid in the reaction solution free of potassium chloride is measured in the same manner, which is subtracted from the inorganic phosphoric acid amount in the presence of potassium chloride to determine the H+, K+-ATPase activity. The inhibitory rate (%) is determined from the activity value of the control and the activity values of various concentrations of the test compound, and the 50% inhibitory concentration (IC50) of the H+, K+-ATPase activity is determined.
動物実験 動物モデル Male Sprague-Dawley rats
投薬量 1, 2, and 4 mg/kg
投与方法 Orally

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。