JP‐1366: A novel and potent potassium‐competitive acid blocker that is effective in the treatment of acid‐related diseases

Abstract

AbstractThe global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long‐term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP‐1366 affected gastric H+/K+‐ATPase activity and used the Na+/K+‐ATPase assay to confirm the selectivity of H+/K+‐ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP‐1366 and TAK‐438 were analyzed by Lineweaver–Burk. Also, we investigated the effects of JP‐1366 in various models involving reflux esophagitis. We found that JP‐1366 mediates strong, selective, and dose‐dependent inhibition of H+/K+‐ATPase. We found that JP‐1366 significantly suppressed gastric acid secretion in histamine‐treated pylorus‐ligated rats in a dose‐dependent manner. Additionally, we confirmed that JP‐1366 inhibited histamine‐stimulated gastric acid secretion in the HPD model. JP‐1366 exhibited a more than 2‐fold higher inhibitory effect on esophageal injury than TAK‐438 in GERD lesions and had a more potent inhibitory effect in indomethacin‐ or aspirin‐induced gastric ulcer rat models than TAK‐438. Additionally, JP‐1366 inhibited gastric ulcers. These results support the possibility that JP‐1366 is a good candidate drug for treating acid‐related diseases.