atovaquone   Click here for help

GtoPdb Ligand ID: 9695

Synonyms: 566C80 | Mepron® | Wellvone®
Approved drug PDB Ligand Antimalarial Ligand
atovaquone is an approved drug (FDA (1992))
Compound class: Synthetic organic
Comment: Atovaquone is a synthetic hydroxynaphthoquinone with broad-spectrum antiprotozoal activity. It is an antimalarial drug and used in combination with proguanil.
Note that we have drawn the molecule as specified by the INN record and ChEMBL entry listed on this summary page. The structure for PubChem CID 74989 (link in table below) is shown without specified stereochemistry (InChi Key BSJMWHQBCZFXBR-UHFFFAOYSA-N).
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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 3
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 54.37
Molecular weight 366.1
XLogP 6.31
No. Lipinski's rules broken 1

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 Clc1ccc(cc1)C1CCC(CC1)C1=C(O)C(=O)c2c(C1=O)cccc2
Isomeric SMILES Clc1ccc(cc1)[C@@H]1CC[C@H](CC1)C1=C(O)C(=O)c2c(C1=O)cccc2
InChI InChI=1S/C22H19ClO3/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26/h1-4,9-13,15,26H,5-8H2/t13-,15-
InChI Key KUCQYCKVKVOKAY-CTYIDZIISA-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/)
No information available.
Summary of Clinical Use Click here for help
Atovaquone is used in combination with proguanil in both the treatment of uncomplicated malaria caused by P. falciparum and in malaria prophylaxis [1-2]. The use of atovaquone as an antimalarial monotherapy is not indicated because of concerns regarding recrudescence rates and parasite resistance [7].
Other uses of atovaquone are as a combined therapy with azithromycin for the treatment of babesiosis [6] and as a monotherapy for the prevention and treatment of mild-to moderate pneumonia caused by P. jirovecii (PCP) in individuals who are sensitive to trimethoprim-sulfamethoazole treatment [5].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The mechanism of action of atovaquone has been studied most extensively in the Plasmodium parasite. The compound inhibits the cytochrome bc1 complex of the mitochondrial electron-transfer chain, with a subsequent collapse of the mitochondrial membrane potential [9-10]. An active cytochrome bc1 complex is necessary for the biosynthesis of pyrimidines and disruption of this pathway is lethal to the parasite [8].
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For extended ADME data see the following:

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