product name Vonoprazan Fumarate (TAK-438)
Description: Vonoprazan Fumarate (also known as 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. In cultured gastric glands, TAK-438 treatment resulted in a longer and stronger acid formation inhibition. The inhibition effect of TAK-438 on acid secretion seemed to be associated with gastric parietal cell physiology.
References: J Pharmacol Exp Ther. 2010 Oct;335(1):231-8; J Pharmacol Exp Ther. 2011 Jun;337(3):797-804.
461.46
Formula
C17H16FN3O2S.C4H4O4
CAS No.
1260141-27-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 62 mg/mL (134.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 17 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: |
|---|---|
| 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. 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. |
| Animal model | Male Sprague-Dawley rats |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose solution; 1, 2, and 4 mg/kg; oral administration |
| References | J Pharmacol Exp Ther. 2010 Oct;335(1):231-8; J Pharmacol Exp Ther. 2011 Jun;337(3):797-804. |
