- Guide to PHARMACOLOGY
Synonyms: GNF156 | KAF156
Compound class: Synthetic organic
Comment: Ganaplacide is the optimised lead for the imidazolopiperazines (IZPs), a novel class of compounds identified from a phenotypic screen as having 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|
|Clinical evaluation of ganaplacide indicates promising activity against uncomplicated P. vivax or P. falciparum infections in adult malaria patients (results from Phase 2b trial NCT01753323 published in ). Recruitment has commenced for a Phase 2 trial for combination therapy with lumefantrine (NCT03167242, last update March, 2021).|
|Mechanism Of Action and Pharmacodynamic Effects|
|Decreased susceptibility to ganaplacide is associated with mutations in three P. falciparum genes, PfCARL (cyclic amine resistance locus), PfUGT (UDP-galactose) and PfACT (Acetyl-CoA transporter), but it is thought that these are involved in broad mechanisms of antimalarial drug resistance and are not considered to be likely targets of the imidazolopiperazines (IZPs) [2,4]. Further investigation has revealed that IZPs may target the Plasmodium intracellular secretory pathway, blocking parasite development by inhibiting protein trafficking, blocking the establishment of new permeation pathways and causing expansion of the endoplasmic reticulum .|
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT03167242||Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria||Phase 2 Interventional||Novartis|
|NCT01753323||Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection||Phase 2 Interventional||Novartis||5|
|Ganaplacide has a mean terminal half-life for elimination of 44.1 hours .|