vonoprazan   Click here for help

GtoPdb Ligand ID: 11549

Synonyms: compound 13e [PMID: 22512618] | TAK-438 | TAK438 | Takecab® | TAKECAB® | Vocinti® | Voquezna®
Approved drug PDB Ligand
vonoprazan is an approved drug (Japan (2014), FDA (2022))
Compound class: Synthetic organic
Comment: Vonoprazan (TAK-438) is a first-in-class, potassium competitive acid blocker (P-CAB) class agent [4,7]. It reduces gastric acid production via reversible inhibition of the gastric proton pump ATPase (a.k.a. gastric H+,K+-ATPase) [1-2,7]. The compound appears to dock within the luminal vestibule of the proton pump's alpha subunit (ATP4A) and prevents K+ access to the ion binding domain, with a Ki of 3 nM for the wild type H+,K+-ATPase [7]. Vonoprazan has a faster onset of action than widely used proton pump inhibitors (PPI), doesn't require acid-mediated activation and provides long-lasting inhibition (due to its slow dissociation rate) of the gastric H+,K+-ATPase [5-6].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 72.37
Molecular weight 345.09
XLogP 2.5
No. Lipinski's rules broken 0
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Canonical SMILES CNCc1cc(n(c1)S(=O)(=O)c1cccnc1)c1ccccc1F
Isomeric SMILES CNCc1cc(n(c1)S(=O)(=O)c1cccnc1)c1ccccc1F
InChI InChI=1S/C17H16FN3O2S/c1-19-10-13-9-17(15-6-2-3-7-16(15)18)21(12-13)24(22,23)14-5-4-8-20-11-14/h2-9,11-12,19H,10H2,1H3
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Summary of Clinical Use Click here for help
Vonoprazan (TAK-438) was progressed to Phase 3 clinical evaluation for non-erosive gastroesophageal reflux disease, gastric, duodenal and peptic ulcers, and erosive esophagitis (erosive gastroesophageal reflux disease, erosive GERD). It was first approved as a monotherapy in Japan in 2015 [3] as a treatment for gastroduodenal ulcer (incl. drug-induced peptic ulcers such as those associated with NSAID administration) and reflux esophagitis. Vonoprazan can be as an adjunct to antibacterials for the eradication of Helicobacter pylori infection. It was approved by the FDA in May 2022, as a component of co-packaged pills called Voquezna® Triple Pak, that contains vonoprazan, amoxicillin, and clarithromycin, and which is indicated for H. pylori eradication. It's also available as a Voquezna® Dual Pak (vonoprazan and amoxicillin). In November 2023, FDA approval was expanded to include single agent treatment/maintenance of healing for erosive GERD and its associated heartburn.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01452776 Long-Term Safety Study of TAK-438 in the Maintenance Treatment of Healed Erosive Esophagitis Phase 3 Interventional Takeda
NCT03050307 Comparison of TAK-438 (Vonoprazan) to Lansoprazole in the Treatment of Gastric Ulcer Participants With or Without Helicobacter Pylori Infection Phase 3 Interventional Takeda
NCT02954848 Phase 3 Study of TAK-438 10 mg in the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD) Phase 3 Interventional Takeda
NCT03050359 Comparison of TAK-438 (Vonoprazan) to Lansoprazole in the Treatment of Duodenal Ulcer Participants With or Without Helicobacter Pylori Infection Phase 3 Interventional Takeda