ArticleAlimentary pharmacology & therapeutics2015
The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+ -ATPase.
Article in Alimentary pharmacology & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 4 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- First-line Eradication of Helicobacter pylori Infection with High-Dose Amoxicillin and Vonoprazan: A Systematic Review and Meta-analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Pooled it
- Efficacy and safety of vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for patients withFrontiers in microbiology · 2025Pooled it
- Effect of potassium-competitive acid blockers on human gut microbiota: a systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Proton pump inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2020Pooled it
- The pharmacokinetics and safety of vonoprazan in adolescents and children with gastroesophageal reflux disease.Journal of pediatric gastroenterology and nutrition · 2026Trial
- Trial
- Effect of Vonoprazan, a Potassium-Competitive Acid Blocker, on theDigestive diseases and sciences · 2017Trial
- Pecan nut-derived carbon quantum dots-modified electrode for sensitive electrochemical determination of vonoprazan using a green analytical approach.Scientific reports · 2026Article
- Evolving landscape of potassium-competitive acid blockers: toward disease-specific use beyond acid suppression.Journal of gastroenterology · 2026Review
- Helicobacter pylori eradication in the face of escalating anti-microbial resistance: Geographic heterogeneity and emerging treatment strategies.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2026Review
- Vonoprazan-Containing Triple Therapy Based on Clarithromycin Susceptibility May Be Definitive Treatment Strategy for Eradication ofJGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Efficacy of a reduced-drug burden quadruple therapy with vonoprazan, cefuroxime, minocycline, and bismuth forFrontiers in medicine · 2026Article
- Optimizing acid-related disease management: insights into potassium-competitive acid blockers and proton pump inhibitors.European journal of clinical pharmacology · 2025Review
- The Efficacy of Potassium-Competitive Acid Blocker Compared With Double Dose of Proton Pump Inhibitor in Patients With Refractory Gastro-Esophageal Reflux Disease: A Case-Control Study.The Korean journal of helicobacter and upper gastrointestinal research · 2025Article
- Awareness, attitudes, and clinical utilization of vonoprazan for Helicobacter pylori infection and gastroesophageal reflux disease among Chinese physicians: a nationwide cross-sectional study.BMC gastroenterology · 2025Article
- Vonoprazan: A Review in Erosive Esophagitis and Non-Erosive Gastro-Esophageal Reflux Disease.Drugs · 2025Review
- Macrophage Membrane-Coated Liposomes Delivering Vonoprazan Disrupt Mitochondrial Oxidative Phosphorylation in Diffuse Large B-Cell Lymphoma.International journal of nanomedicine · 2025Article
- Efficacy of Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors for Gastric Ulcers: Bayesian and Frequentist Network Meta-Analysis With Cross-Inference Through a Quality management System.Current therapeutic research, clinical and experimental · 2025Article
- Evaluating vonoprazan and tegoprazan for gastroesophageal reflux disease treatment in Chinese Healthcare: an EVIDEM framework analysis.BMC gastroenterology · 2024Article
- Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or withoutPharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe gastric H(+) ,K(+) -ATPase is the preferred target for acid suppression. Until recently, the only drugs that effectively inhibited this ATPase were the proton pump inhibitors (PPIs). PPIs are acid-activated prodrugs that require acid protection. Once acid-activated, PPIs bind to cysteines of the ATPase, resulting in covalent, long-lasting inhibition. The short plasma half-life of PPIs and continual de novo synthesis of the H(+) ,K(+) -ATPase result in difficulty controlling night-time acid secretion. A new alternative to PPIs is the pyrrolo-pyridine, vonoprazan (TAK-438), a potassium-competitive acid blocker (PCAB) that does not require acid protection. In contrast to other PCABs, vonoprazan has a long duration of action, resulting in 24-h control of acid secretion, a high pKa of 9.37 and high affinity (Ki = 3.0 ηmol/L).
aimTo determine binding selectivity of vonoprazan for the gastric H(+) ,K(+) -ATPase and to explain its slow dissociation.
methodsGastric gland and parietal cell binding of vonoprazan was determined radiometrically. Molecular modelling explained the slow dissociation of vonoprazan from the H(+) ,K(+) -ATPase.
resultsVonoprazan binds selectively to the parietal cell, independent of acid secretion. Vonoprazan binds in a luminal vestibule between the surfaces of membrane helices 4, 5 and 6. Exit of the drug to the lumen is hindered by asp137 and asn138 in the loop between TM1 and TM2, which presents an electrostatic barrier to movement of the sulfonyl group of vonoprazan. This may explain its slow dissociation from the H(+) ,K(+) -ATPase and long-lasting inhibition.
conclusionThe binding model provides a template for design of novel potassium-competitive acid blockers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.