mefloquine   Click here for help

GtoPdb Ligand ID: 4252

Synonyms: GNF-Pf-5544 | Lariam® | Ro-21-5998-001 | WR-142490
Approved drug PDB Ligand Antimalarial Ligand
mefloquine is an approved drug (FDA (1989), UK (1989))
Compound class: Synthetic organic
Comment: Mefloquine belongs to the aryl amino alcohols, a chemical class of antimalarial drugs that includes quinine, lumefantrine and halofantrine.
The approved drug is a racemic mixture of (R,S)- and (S,R)-enantiomers. We show the chemical structure without stereochemistry to represent the mixture and the non-isomeric structure is also represented in the PubChem and ChEMBL entries listed in the links table below, while the two enantiomers forming the racemate are represented by PubChem CID 40692 and PubChem CID 456309. PubChem lists 9 stereoisotopes.
The administerd form contains the mefloquine hydrochloride salt.

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.

Activity at non-malarial protein targets:
Racemic mefloquine has been identified as an antagonist of the human adenosine A2A and A1 receptors, with nanomolar binding affinities [8]. The (11R,2'S) isomer of mefloquine (PubChem CID 456309) has been determined as the most potent A2A binder, with a Ki of 61 nM (Ki vs. A1 receptor is 255 nM) [4]. It has been suggested that off-target activity at human adenosine receptors may contribute towards the adverse neuropsychiatric side-effects that are associated with mefloquine use.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 45.15
Molecular weight 378.12
XLogP 3.87
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES OC(c1cc(nc2c1cccc2C(F)(F)F)C(F)(F)F)C1CCCCN1
Isomeric SMILES OC(c1cc(nc2c1cccc2C(F)(F)F)C(F)(F)F)C1CCCCN1
InChI InChI=1S/C17H16F6N2O/c18-16(19,20)11-5-3-4-9-10(15(26)12-6-1-2-7-24-12)8-13(17(21,22)23)25-14(9)11/h3-5,8,12,15,24,26H,1-2,6-7H2
InChI Key XEEQGYMUWCZPDN-UHFFFAOYSA-N
Bioactivity Comments
The interaction table below provides data from an evaluation of the antimalarial (asexual blood stage) activity of mefloquine, using a panel of P. falciparum strains. Mefloquine demonstrates no evidence of reduced potency against drug resistant strains. Note that the whole organism assay data provided below relates to use of the racemic mixture.
Selectivity at GPCRs
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
A2A receptor Hs Antagonist Antagonist 7.0 pKi - 8
pKi 7.0 (Ki 1.04x10-7 M) [8]
Description: Binding affinity determined by displacement of [3H]-CGS21680 from human A2A receptors by increasing concentrations of racemic mefloquine.
A1 receptor Hs Antagonist Antagonist 6.2 pKi - 8
pKi 6.2 (Ki 6.75x10-7 M) [8]
Description: Binding affinity determined by displacement of [3H]-DPCPX from human A1 receptors by increasing concentrations of racemic mefloquine.
Selectivity at ion channels
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
VRAC Hs Channel blocker - - - -
Selectivity at other protein targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Plasmodium falciparum purine nucleoside phosphorylase Pf Inhibitor - 5.2 pKi - 3
pKi 5.2 (Ki 5.9x10-6 M) [3]
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA Pf7G8 Parasite growth inhibition assay - - 8.5 pIC50 - 2
pIC50 8.5 (IC50 3x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfK1 Parasite growth inhibition assay - - 8.4 pIC50 - 2
pIC50 8.4 (IC50 3.8x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfW2 Parasite growth inhibition assay - - 8.4 pIC50 - 2
pIC50 8.4 (IC50 4.4x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfV1/S Parasite growth inhibition assay - - 8.2 pIC50 - 2
pIC50 8.2 (IC50 5.7x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfD6 Parasite growth inhibition assay - - 8.1 pIC50 - 2
pIC50 8.1 (IC50 8.8x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfNF54 Parasite growth inhibition assay - - 8.0 pIC50 - 2
pIC50 8.0 (IC50 1.07x10-8 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfTM90C2A Parasite growth inhibition assay - - 7.8 pIC50 - 2
pIC50 7.8 (IC50 1.45x10-8 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
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