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Updated: Sep 9, 2025

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
[Current status and prospects of using potassium-competitive acid blockers in gastroenterology]
I V Maev1, D N Andreev1, A V Zaborovsky1
1Russian University of Medicine.
Abstract:
Over the past decades, acid production in the stomach has been regulated mainly by proton pump inhibitors (PPIs). However, despite their widespread use and solid evidence base for efficacy, PPIs have pharmacokinetic and pharmacodynamic limitations, such as a slow onset of action, response variability (dependent on CYP2C19 polymorphisms), and the need for activation in an acidic environment. These restrictions underscore the need for innovative molecular approaches to inhibiting acid production, which led to the development of a fundamentally different mechanism of action - potassium-competitive acid blockers (P-CABs), first introduced into clinical practice in 2015. The mechanism of action of P-CABs is based on a reversible ionic interaction with hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) in parietal cells of the stomach. Direct inhibition of the active enzyme enables more rapid and sustained control of gastric secretion, including nocturnal and postprandial acid production, making this class of drugs particularly relevant in the treatment of gastroesophageal reflux disease, peptic ulcers, and in the eradication of Helicobacter pylori. Recent meta-analyses demonstrate the clinical benefits of P-CABs over PPIs for these indications.
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