Abstract

Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H⁺/K⁺-ATPase. Tegoprazan inhibited porcine, canine, and human H⁺/K⁺-ATPases in vitro with IC₅₀ values ranging from 0.29 to 0.52 μM, while that for canine kidney Na⁺/K⁺-ATPase was more than 100 μM. A kinetic analysis revealed that tegoprazan inhibited H⁺/K⁺-ATPase in a potassium-competitive manner and the binding was reversible. Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs were well absorbed into the blood stream and distributed in gastric tissue/fluid higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg starting from 1 hour after administration. Moreover, an oral administration of tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a gastric phase III contraction of the migrating motor complex in pentagastrin-treated dogs and similar effects was observed with the other P-CAB, vonoprazan. Tegoprazan is the novel P-CAB that may provide a new option for the therapy of gastric acid–related and motility-impaired diseases.