ganaplacide

Ligand id: 9946

Name: ganaplacide

Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 76.18
Molecular weight 411.19
XLogP 4.09
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

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 [4]). Recruitment has commenced for a Phase 2 trial for combination therapy with lumefantrine (NCT03167242, last update January, 2020).
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 [2-3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
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
NCT03167242 Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2 Interventional Novartis
Pharmacokinetics
Elimination
Ganaplacide has a mean terminal half-life for elimination of 44.1 hours [4].