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KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission

Kuhen, Kelli L. and Chatterjee, Arnab K. and Rottmann, Matthias and Gagaring, Kerstin and Borboa, Rachel and Buenviaje, Jennifer and Chen, Zhong and Francek, Carolyn and Wu, Tao and Nagle, Advait and Barnes, S. Whitney and Plouffe, David and Lee, Marcus C. S. and Fidock, David A. and Graumans, Wouter and van de Vegte-Bolmer, Marga and van Gemert, Geert J. and Wirjanata, Grennady and Sebayang, Boni and Marfurt, Jutta and Russell, Bruce and Suwanarusk, Rossarin and Price, Ric N. and Nosten, Francois and Tungtaeng, Anchalee and Gettayacamin, Montip and Sattabongkot, Jetsumon and Taylor, Jennifer and Walker, John R. and Tully, David and Patra, Kailash P. and Flannery, Erika L. and Vinetz, Joseph M. and Renia, Laurent and Sauerwein, Robert W. and Winzeler, Elizabeth A. and Glynne, Richard J. and Diagana, Thierry T.. (2014) KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrobial agents and chemotherapy, Vol. 58, H. 9. pp. 5060-5067.

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Official URL: http://edoc.unibas.ch/dok/A6298864

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Rottmann, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:28
Deposited On:07 Nov 2014 08:28

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