- Guide to PHARMACOLOGY
Compound class: Synthetic organic
Comment: MMV048 is the optimised lead compound for the 2-aminopyridines, a class of small molecules with promising antimalarial activity .
The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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.✖
|No information available.|
|Summary of Clinical Use|
|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|
|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 . This lipid kinase has been proposed to act at the Golgi to regulate essential membrane trafficking events .|
|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|
|The elimination half-life of MMV048 has a predicted value of 90 hours .|