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 [3].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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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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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 activitity 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 Pf None Binding 6.5 – 7.0 pKd - 2
pKd 7.0 (Kd 1x10-7 M) [2]
pKd 6.5 (Kd 3x10-7 M) [2]
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Plasmodium falciparum phosphatidylinositol 4-kinase PfNF54 Parasite growth inhibition assay - - 7.6 pIC50 - 2
pIC50 7.6 (IC50 2.8x10-8 M) [3H]-hypoxanthine incorporation assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum phosphatidylinositol 4-kinase Pf Standard membrane feeding assay (SMFA) - - 6.9 pIC50 - 2
pIC50 6.9 (IC50 1.11x10-7 M) Indirect SMFA [2]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
Plasmodium falciparum phosphatidylinositol 4-kinase PfNF54 Parasite gametocyte viability assay - - 6.6 – 6.8 pIC50 - 2
pIC50 6.8 (IC50 1.4x10-7 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [2]
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 [2]
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 [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Plasmodium falciparum phosphatidylinositol 4-kinase Pc Parasite liver stage assay - - 5.0 – 7.2 pIC50 - 2
pIC50 7.2 (IC50 6.1x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [2]
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) [2]
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) [2]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)