ArticleAntimicrobial agents and chemotherapy2016
PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
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- A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inbioRxiv : the preprint server for biology · 2024Article
- Transfection Models to InvestigatePathogens (Basel, Switzerland) · 2023Review
- Ethiopian Plasmodium vivax hypnozoites formation dynamics and their susceptibility to reference antimalarial drugs.BMC infectious diseases · 2023Article
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- Non-Human Primate Malaria Infections: A Review on the Epidemiology in Malaysia.International journal of environmental research and public health · 2022Review
- Metabolic, Pharmacokinetic, and Activity Profile of the Liver Stage Antimalarial (RC-12).ACS omega · 2022Article
- A Phenotypic Screen for the Liver Stages ofBio-protocol · 2021Article
- Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro.Scientific reports · 2021Article
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- Review
- Chloroquine Potentiates Primaquine Activity against Active and Latent Hepatic PlasmodiaAntimicrobial agents and chemotherapy · 2020Article
- Plasmodium vivax Liver and Blood Stages Recruit the Druggable Host Membrane Channel Aquaporin-3.Cell chemical biology · 2020Article
- Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds.Analytical chemistry · 2020Article
- Hemocyte phagosomal proteome is dynamically shaped by cytoskeleton remodeling and interorganellar communication with endoplasmic reticulum during phagocytosis in a marine invertebrate, Crassostrea gigas.Scientific reports · 2020Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Two Plasmodium PI4 kinase (PI4K) inhibitors, KDU691 and LMV599, were selected for in vivo testing as causal prophylactic and radical-cure agents for Plasmodium cynomolgi sporozoite-infected rhesus macaques, based on their in vitro activity against liver stages. Animals were infected with P. cynomolgi sporozoites, and compounds were dosed orally. Both the KDU691 and LMV599 compounds were fully protective when administered prophylactically, and the more potent compound LMV599 achieved protection as a single oral dose of 25 mg/kg of body weight. In contrast, when tested for radical cure, five daily doses of 20 mg/kg of KDU691 or 25 mg/kg of LMV599 did not prevent relapse, as all animals experienced a secondary infection due to the reactivation of hypnozoites in the liver. Pharmacokinetic data show that LMV599 achieved plasma exposure that was sufficient to achieve efficacy based on our in vitro data. These findings indicate that Plasmodium PI4K is a potential drug target for malaria prophylaxis but not radical cure. Longer in vitro culture systems will be required to assess these compounds' activity on established hypnozoites and predict radical cure in vivo.
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