生物活性

• 靶点	H+/K+ ATPase IC50:19nM

• 描述The potassium-competitive acid blocker (P-CAB), a new class of acid suppressant, inhibits gastric H⁺,K⁺-ATPase activity by reversible and K⁺-competitive ionic binding to the enzyme. TAK-438 is a novel P-CAB that reversibly inhibits H⁺,K⁺-ATPase with IC₅₀ of 19 nM (pH 6.5), and exhibits potent gastric acid secretion inhibitory action in vivo. And TAK-438 was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases . Under weakly acidic conditions (pH 6.5), TAK-438 inhibited gastric H⁺,K⁺-ATPase activity in a concentration-dependent manner. Under neutral conditions (pH 7.5), the inhibitory activity of TAK-438 was almost the same as that under weakly acidic conditions. In Pylorus-Ligated rats, TAK-438 at doses of 0.5, 1, 2, and 4 mg/kg inhibited basal gastric acid secretion in a dose-dependent manner, and the ID₅₀ value was 1.26 mg/kg. In Anesthetized rats, TAK-438 inhibited 2DG-stimulated gastric acid secretion in a dose-dependent manner, and the ID_{50 value of TAK-438 was 0.83 mg/kg. TAK-438 completely inhibited gastric acid secretion at the 4 mg/kg dose .}
• 作用机制TAK-438 inhibited gastric H⁺,K⁺-ATPase in a K⁺-competitive manner .