chloroquine   Click here for help

GtoPdb Ligand ID: 5535

Synonyms: Aralen® | chloraquine | Malaquin®
Approved drug PDB Ligand Immunopharmacology Ligand Antimalarial Ligand
chloroquine is an approved drug (FDA (1949), UK (2000))
Compound class: Synthetic organic
Comment: Chloroquine is a 4-aminoquinoline and used primarily as an antimalarial drug.
The approved drug is a racemic mixture and we show the chemical structure without stereochemistry to represent the mixture. The non-isomeric structure is also represented in the PubChem, ChEMBL and ChEBI entries listed in the links table below, while the two enantiomers forming the racemate are represented by PubChem CID 444810 and PubChem CID 639540. The PDB entry listed in the links table is for (R)-chloroquine.
Marketed formulations may contain chloroquine phosphate (PubChem CID 64927).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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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 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 8
Topological polar surface area 28.16
Molecular weight 319.18
XLogP 4.27
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 CCN(CCCC(Nc1ccnc2c1ccc(c2)Cl)C)CC
Isomeric SMILES CCN(CCCC(Nc1ccnc2c1ccc(c2)Cl)C)CC
InChI InChI=1S/C18H26ClN3/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21)
InChI Key WHTVZRBIWZFKQO-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/)
Bioactivity Comments
Chloroquine is active against only the erythrocytic forms of P. vivax, P. malariae, and susceptible strains of P. falciparum (but not the gametocytes of P. falciparum).
In humans, chloroquine inhibits thiamine uptake acting specifically on thiamine transporter 2 (SLC19A3).

Chloroquine is one of a number of drugs that are cationic amphiphilic in nature, for which anti-SARS-CoV-2 activity has been identified in drug repurposing screens. Tummino et al. (2021; bioRxiv preprint PMID: 33791693 target="_blank") suggest that this antiviral activity is most likely a result of the drug promoting phospholipidosis via disruption of lipid homeostasis.
Selectivity at GPCRs
Key to terms and symbols Click on species/strain names for details Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
MRGPRX1 Hs Agonist Agonist 3.5 pEC50 - 2
⤷ pEC50 3.5 (EC50 2.97x10-4 M) [2]
TAS2R3 Hs Agonist Agonist - - - 3
⤷ [3]
Description: Threshold=10 μM
Whole organism assay data
Key to terms and symbols Click on species/strain names for details Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA PfD6

Plasmodium falciparum D6

P. falciparum strain D6 (PfD6) was collected in Sierra Leone.
PfD6 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is generally considered drug sensitive with minor mefloquine resistance.
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 Parasite growth inhibition assay - - 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 8.8x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfNF54

Plasmodium falciparum NF54

P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands.
PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite growth inhibition assay - - 7.9 pIC50 - 1
⤷ pIC50 7.9 (IC50 1.12x10-8 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pf7G8

Plasmodium falciparum 7G8

P. falciparum strain 7G8 (Pf7G8) was subcloned from the IMTM22 strain by limiting dilution. The original IMTM22 strain was isolated from a 12 year old male near Manaus, Brazil in 1980.
Pf7G8 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4). This strain is a gametocyte producer and is reported to be chloroquine-sensitive and pyrimethamine-resistant.
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 Parasite growth inhibition assay - - 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 7.03x10-8 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfTM90C2A

Plasmodium falciparum TM90C2A

P. falciparum TM90C2A (PfTM90C2A) is a clinical isolate, first described during a Phase 2 clinical trial to determine atovaquone efficacy in Thailand (PMID:8651372). PfTM90C2A is sensitive to atovaquone.
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 Parasite growth inhibition assay - - 7.0 pIC50 - 1
⤷ pIC50 7.0 (IC50 1.058x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfK1

Plasmodium falciparum K1

P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979.
PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain.
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 Parasite growth inhibition assay - - 6.7 pIC50 - 1
⤷ pIC50 6.7 (IC50 1.98x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfW2

Plasmodium falciparum W2

P. falciparum strain W2 (PfW2) was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfW2 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and susceptible to mefloquine.
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 Parasite growth inhibition assay - - 6.6 pIC50 - 1
⤷ pIC50 6.6 (IC50 2.683x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfV1/S

Plasmodium falciparum V1/S

P. falciparum strain V1/S (PfV1/S) is an in vitro culture-adapted clone of V1, that originated in Vietnam.
PfV1/S can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and quinine.
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 Parasite growth inhibition assay - - 6.5 pIC50 - 1
⤷ pIC50 6.5 (IC50 3.04x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)