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
Bioactivity Comments
Competitive binding assays show that MMV048 inhibits the binding of a single protein, PfPI4K. The antiparasite activity of MMV048 against all Plasmodium lifecycle stages is also provided in the interaction table below.
Selectivity at other protein targets
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
Plasmodium falciparum phosphatidylinositol 4-kinase beta Pf

Plasmodium falciparum

P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa.
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 None Binding 6.5 – 7.0 pKd - 3
⤷ pKd 7.0 (Kd 1x10-7 M) [3]
pKd 6.5 (Kd 3x10-7 M) [3]
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
Plasmodium falciparum phosphatidylinositol 4-kinase beta 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 - - 7.6 pIC50 - 3
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [3H]-hypoxanthine incorporation assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum phosphatidylinositol 4-kinase beta Pf

Plasmodium falciparum

P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa.
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 Standard membrane feeding assay (SMFA) - - 6.9 pIC50 - 3
⤷ pIC50 6.9 (IC50 1.11x10-7 M) Indirect SMFA [3]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
Plasmodium falciparum phosphatidylinositol 4-kinase beta 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 gametocyte viability assay - - 6.6 – 6.8 pIC50 - 3
⤷ pIC50 6.8 (IC50 1.4x10-7 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pIC50 6.7 (IC50 2.14x10-7 M) Parasite early stage (I-III) gametocyte assay using luciferase reporter line [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pIC50 6.6 (IC50 2.85x10-7 M) Parasite late stage (IV-V) gametocyte assay: parasitic lactate dehydrogenase (pLDH) assay [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Plasmodium falciparum phosphatidylinositol 4-kinase beta Pc

Plasmodium cynomolgi

P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite).
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 Parasite liver stage assay - - 5.0 – 7.2 pIC50 - 3
⤷ pIC50 7.2 (IC50 6.1x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [3]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
pIC50 7.2 (IC50 6.4x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [3]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
pIC50 <5.0 (IC50 >1x10-5 M) P. cynomolgi assay to assess elimination of hypnozoites (potential as a radical cure) [3]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)