ArticleThe Journal of pharmacology and experimental therapeutics2011
Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438).
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 3 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 146 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
- Direct Comparison of the Efficacy and Safety of Vonoprazan Versus Proton-Pump Inhibitors for Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.Digestive diseases and sciences · 2021Pooled it
- Pooled it
- Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.BMC gastroenterology · 2023Trial
- The Effect of Food on the Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan.Clinical pharmacology in drug development · 2022Trial
- Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucossal dissection: a randomized, open-label trial.BMC gastroenterology · 2021Trial
- Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects.Clinical drug investigation · 2021Trial
- Trial
- A prospective randomized trial of a potassium competitive acid blocker vs proton pump inhibitors on the effect of ulcer healing after endoscopic submucosal dissection of gastric neoplasia.The Journal of international medical research · 2019Trial
- Trial
- Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study.Gut · 2018Trial
- Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children.Journal of gastroenterology · 2018Trial
- Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan with lansoprazole.World journal of gastroenterology · 2018Trial
- Effect of Vonoprazan, a Potassium-Competitive Acid Blocker, on theDigestive diseases and sciences · 2017Trial
- Pharmacokinetic Drug-Drug Interactions Between Vonoprazan and Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drugs: A Phase 2, Open-Label, Study in Healthy Japanese Men.Clinical drug investigation · 2017Trial
- Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.Alimentary pharmacology & therapeutics · 2017Trial
- Trial
- Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis.Alimentary pharmacology & therapeutics · 2016Trial
- Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.Alimentary pharmacology & therapeutics · 2015Trial
- Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects.Alimentary pharmacology & therapeutics · 2015Trial
18 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibition of the gastric H,K-ATPase by the potassium-competitive acid blocker (P-CAB) 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine (TAK-438), is strictly K(+)-competitive with a K(i) of 10 nM at pH 7. In contrast to previous P-CABs, this structure has a point positive charge (pK(a) 9.06) allowing for greater accumulation in parietal cells compared with previous P-CABs [e.g., (8-benzyloxy-2-methyl-imidazo(1,2-a)pyridin-3-yl)acetonitrile (SCH28080), pK(a) 5.6]. The dissociation rate of the compound from the isolated ATPase is slower than other P-CABs, with the t(1/2) being 7.5 h in 20 mM KCl at pH 7. The stoichiometry of binding of TAK-438 to the H,K-ATPase is 2.2 nmol/mg in the presence of Mg-ATP, vanadate, or MgP(i). However, TAK-438 also binds enzyme at 1.3 nmol/mg in the absence of Mg(2+). Modeling of the H,K-ATPase to the homologous Na,K-ATPase predicts a close approach and hydrogen bonding between the positively charged N-methylamino group and the negatively charged Glu795 in the K(+)-binding site in contrast to the planar diffuse positive charge of previous P-CABs. This probably accounts for the slow dissociation and high affinity. The model also predicts hydrogen bonding between the hydroxyl of Tyr799 and the oxygens of the sulfonyl group of TAK-438. A Tyr799Phe mutation resulted in a 3-fold increase of the dissociation rate, showing that this hydrogen bonding also contributes to the slow dissociation rate. Hence, this K(+)-competitive inhibitor of the gastric H,K-ATPase should provide longer-lasting inhibition of gastric acid secretion compared with previous drugs of this class.
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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.