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

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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Selectivity at transporters
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
ATP4A Pig Inhibitor Inhibition 7.7 pIC50 - 2
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [2]
Description: Inhibition of H+/K+-ATPase activity in a gastric mucosal membrane microsomal fraction from pig stomach.
Ligand mentioned in the following text fields
H+/K+-ATPases comments