ELQ-300   Click here for help

GtoPdb Ligand ID: 10021

Synonyms: ELQ300
Antimalarial Ligand
Compound class: Synthetic organic
Comment: ELQ-300 is a late lead candidate from a novel class of 4(1H)-quinolone-based compounds with potent antimalarial activity [4]. The ELQs (endochin-like quinolones) are structural derivatives of endochin (PubChem CID 100474), which has potent antiplasmodial activity, but is highly metabolically unstable in mammals [1,6].

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 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 1
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 60.55
Molecular weight 475.08
XLogP 8.16
No. Lipinski's rules broken 1
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 COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
Isomeric SMILES COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
InChI InChI=1S/C24H17ClF3NO4/c1-13-22(23(30)18-11-19(25)21(31-2)12-20(18)29-13)14-3-5-15(6-4-14)32-16-7-9-17(10-8-16)33-24(26,27)28/h3-12H,1-2H3,(H,29,30)
InChI Key WZDNKHCQIZRDKW-UHFFFAOYSA-N
References
1. Cross RM, Monastyrskyi A, Mutka TS, Burrows JN, Kyle DE, Manetsch R. (2010)
Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity.
J Med Chem, 53 (19): 7076-94. [PMID:20828199]
2. Frueh L, Li Y, Mather MW, Li Q, Pou S, Nilsen A, Winter RW, Forquer IP, Pershing AM, Xie LH et al.. (2017)
Alkoxycarbonate Ester Prodrugs of Preclinical Drug Candidate ELQ-300 for Prophylaxis and Treatment of Malaria.
ACS Infect Dis, 3 (10): 728-735. [PMID:28927276]
3. Miley GP, Pou S, Winter R, Nilsen A, Li Y, Kelly JX, Stickles AM, Mather MW, Forquer IP, Pershing AM et al.. (2015)
ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.
Antimicrob Agents Chemother, 59 (9): 5555-60. [PMID:26124159]
4. Nilsen A, LaCrue AN, White KL, Forquer IP, Cross RM, Marfurt J, Mather MW, Delves MJ, Shackleford DM, Saenz FE et al.. (2013)
Quinolone-3-diarylethers: a new class of antimalarial drug.
Sci Transl Med, 5 (177): 177ra37. [PMID:23515079]
5. Stickles AM, de Almeida MJ, Morrisey JM, Sheridan KA, Forquer IP, Nilsen A, Winter RW, Burrows JN, Fidock DA, Vaidya AB et al.. (2015)
Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum.
Antimicrob Agents Chemother, 59 (4): 1977-82. [PMID:25605352]
6. Winter R, Kelly JX, Smilkstein MJ, Hinrichs D, Koop DR, Riscoe MK. (2011)
Optimization of endochin-like quinolones for antimalarial activity.
Exp Parasitol, 127 (2): 545-51. [PMID:21040724]