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
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 (Jan 2017) while NCT02880241, to determine the activity against P. vivax and P. falciparum, has been suspended pending analysis of intermediary data (Jan 2018).
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 [2]. This lipid kinase has been proposed to act at the Golgi to regulate essential membrane trafficking events [1].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02783833 MMV390048 and Its Antimalarial Activity Against Plasmodium Falciparum in Healthy Adult Subjects, Part B Phase 1/Phase 2 Interventional Medicines for Malaria Venture
NCT02880241 MMV390048 POC in Patients With P. Vivax and P. Falciparum Malaria Phase 2 Interventional Medicines for Malaria Venture
Pharmacokinetics Click here for help
Elimination
The elimination half-life of MMV048 has a predicted value of 90 hours [2].