MMV048   Click here for help

GtoPdb Ligand ID: 9726

Synonyms: MMV390048
Antimalarial Ligand
Compound class: Synthetic organic
Comment: MMV048 is the optimised lead compound for the 2-aminopyridines, a class of small molecules with promising antimalarial activity [4].

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 5
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 94.32
Molecular weight 393.08
XLogP 3.84
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 Nc1ncc(cc1c1ccc(nc1)C(F)(F)F)c1ccc(cc1)S(=O)(=O)C
Isomeric SMILES Nc1ncc(cc1c1ccc(nc1)C(F)(F)F)c1ccc(cc1)S(=O)(=O)C
InChI InChI=1S/C18H14F3N3O2S/c1-27(25,26)14-5-2-11(3-6-14)13-8-15(17(22)24-10-13)12-4-7-16(23-9-12)18(19,20)21/h2-10H,1H3,(H2,22,24)
InChI Key RTJQABCNNLMCJF-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
MMV048 demonstrates promise as a prophylactic and chemoprotective antimalarial drug but is unlikely to provide a radical cure. The compound has progressed to Phase 2 clinical evaluation. NCT02783833, a trial to determine the minimum inhibitory concentration of MMV048 for the treatment of malaria caused by P. falciparum, has been completed [1] while NCT02880241, to determine the activity against P. vivax and P. falciparum, has been terminated due to a Medicines for Malaria Venture (MMV) strategic business decision (Dec 2020).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The molecular target of MMV048 was first indicated by the identification of resistance conferring mutations in PfPI4K and further investigated using competitive binding assays to show that MMV048 inhibits the binding of only a single protein, PfPI4K [3]. This lipid kinase has been proposed to act at the Golgi to regulate essential membrane trafficking events [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02880241 MMV390048 POC in Patients With P. Vivax and P. Falciparum Malaria Phase 2 Interventional Medicines for Malaria Venture
NCT02783833 MMV390048 and Its Antimalarial Activity Against Plasmodium Falciparum in Healthy Adult Subjects, Part B Phase 1/Phase 2 Interventional Medicines for Malaria Venture 1
Pharmacokinetics Click here for help
Elimination
The elimination half-life of MMV048 has a range of approximately 129 to 215 hours [1].