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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key BFDBKMOZYNOTPK-UHFFFAOYSA-N
No information available.
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