ArticleAntimicrobial agents and chemotherapy2014
KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 69 citations in OpenAlex.
- Safety, Pharmacokinetics, and Causal Prophylactic Efficacy of KAF156 in a Plasmodium falciparum Human Infection Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- In vitro cultured malaria hypnozoites leave a footprint of specific metabolites.PLoS pathogens · 2025Article
- Identification of novel compounds with prophylactic activity against hypnozoites using aAntimicrobial agents and chemotherapy · 2025Article
- Dose-fractionation studies of aAntimicrobial agents and chemotherapy · 2024Article
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- Transfection Models to InvestigatePathogens (Basel, Switzerland) · 2023Review
- Sterile protection against relapsing malaria with a single-shot vaccine.NPJ vaccines · 2022Article
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- Metabolic, Pharmacokinetic, and Activity Profile of the Liver Stage Antimalarial (RC-12).ACS omega · 2022Article
- The Novel bis-1,2,4-Triazine MIPS-0004373 Demonstrates Rapid and Potent Activity against All Blood Stages of the Malaria Parasite.Antimicrobial agents and chemotherapy · 2021Article
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- Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges.BioMed research international · 2021Review
- Chloroquine Potentiates Primaquine Activity against Active and Latent Hepatic PlasmodiaAntimicrobial agents and chemotherapy · 2020Article
- Article
- Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds.Analytical chemistry · 2020Article
- Modeling Relapsing Malaria: Emerging Technologies to Study Parasite-Host Interactions in the Liver.Frontiers in cellular and infection microbiology · 2020Review
- A dual fluorescentCommunications biology · 2020Article
- Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages.Nature communications · 2019Article
- The antimalarial screening landscape-looking beyond the asexual blood stage.Current opinion in chemical biology · 2019Review
- TheeLife · 2019Article
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Authors and funding
26 authors at 7 institutions in 4 countries.
Funding
Abstract
Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure.
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