@article{3ddd0880927e4f13b13ccadb98b0c50b,
title = "KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission",
abstract = "Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50{\%} inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99{\%} effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria.",
keywords = "antimalarial agent, artesunate, chloroquine, imidazole derivative, kaf 156, kaf156, mefloquine, piperazine derivative, unclassified drug, KAF156, animal experiment, animal model, Anopheles, antimalarial activity, antimalarial drug susceptibility, article, controlled study, disease elimination, dose time effect relation, drug dose comparison, drug efficacy, drug safety, female, genetic strain, human, human cell, IC 50, in vitro study, in vivo study, malaria control, malaria falciparum, mouse, multiple drug dose, nonhuman, parasite clearance, parasite transmission, Plasmodium falciparum, Plasmodium vivax malaria, priority journal, rodent malaria, schizont, single drug dose, sporozoite, treatment response, animal, drug effects, IC50, Institute for Cancer Research mouse, Malaria, Falciparum, transmission, Animals, Antimalarials, Imidazoles, Inhibitory Concentration 50, Mice, Mice, Inbred ICR, Piperazines, Sporozoites",
author = "Kuhen, {Kelli L.} and Chatterjee, {Arnab K.} and Matthias Rottmann and Kerstin Gagaring and Rachel Borboa and Jennifer Buenviaje and Zhong Chen and Carolyn Francek and Tao Wu and Advait Nagle and Barnes, {S. Whitney} and David Plouffe and Lee, {Marcus C.S.} and Fidock, {David A.} and Wouter Graumans and {Van De Vegte-Bolmer}, Marga and {Van Gemert}, {Geert J.} and Grennady Wirjanata and Boni Sebayang and Jutta Marfurt and Bruce Russell and Rossarin Suwanarusk and Price, {Ric N.} and Francois Nosten and Anchalee Tungtaeng and Montip Gettayacamin and Jetsumon Sattabongkot and Jennifer Taylor and Walker, {John R.} and David Tully and Patra, {Kailash P.} and Flannery, {Erika L.} and Vinetz, {Joseph M.} and Laurent Renia and Sauerwein, {Robert W.} and Winzeler, {Elizabeth A.} and Glynne, {Richard J.} and Diagana, {Thierry T.}",
year = "2014",
doi = "10.1128/AAC.02727-13",
language = "English",
volume = "58",
pages = "5060--5067",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "9",
}