M5717   Click here for help

GtoPdb Ligand ID: 9737

Synonyms: DDD107498 | DDD498 | MMV121
Antimalarial Ligand
Compound class: Synthetic organic
Comment: M5717 (formerly DDD498) is a quinoline-4-carboxamide derivative that is the optimised lead developed from a phenotypic screen for novel antimalarial drugs and has advanced to clinical evaluation. The compound was awarded MMV Project of the Year (2014).

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 6
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 57.7
Molecular weight 462.24
XLogP 3.43
No. Lipinski's rules broken 0
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 Fc1ccc2c(c1)c(cc(n2)c1ccc(cc1)CN1CCOCC1)C(=O)NCCN1CCCC1
Isomeric SMILES Fc1ccc2c(c1)c(cc(n2)c1ccc(cc1)CN1CCOCC1)C(=O)NCCN1CCCC1
InChI InChI=1S/C27H31FN4O2/c28-22-7-8-25-23(17-22)24(27(33)29-9-12-31-10-1-2-11-31)18-26(30-25)21-5-3-20(4-6-21)19-32-13-15-34-16-14-32/h3-8,17-18H,1-2,9-16,19H2,(H,29,33)
InChI Key BENUHBSJOJMZEE-UHFFFAOYSA-N
Guide to Malaria Pharmacology Comments
M5717 has comparable activity against multiple stages of the malaria parasite lifecycle and is indicated for use as a combination therapy for acute uncomplicated malaria, with potential to be a single-exposure radical cure (SERC) treatment [1]. Preclinical asessment of M5717 in combination with pyronaridine, reports rapid clearance of asexual blood stage parasites with exoerythrocytic activity and shows promise as an effective, long-lasting antimalarial therapy [4].
The compound is example 1A from patent WO2013153357 [2].

Potential Target/Mechanism Of Action: Evidence from genetic experiments indicates that P. falciparum elongation factor 2 (PfeEF2) may be the molecular target [1].
Target Candidate Profiles
Profile Intended Use Target Stage Comment References
TCP-1 reduce parasite burden asexual blood stages 1
TCP-4 chemoprotection hepatic schizonts 1
TCP-5 transmission reduction gametocytes 1