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Reference: Kuhen, KL, Chatterjee, AK, Rottmann, M et al., (2014). KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrobial agents and chemotherapy, 58 (9), 5060-5067.Citable link to this page:

 

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.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Wellcome Trust   Funder: Medicines for Malaria Venture   Funder: Singapore Immunology Network   Funder: Agency for Science,Technology, and Research   Notes:Copyright © 2014 Kuhen et al.This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.

Bibliographic Details

Publisher: American Society for Microbiology

Publisher Website: http://www.asm.org/

Journal: Antimicrobial agents and chemotherapysee more from them

Publication Website: http://aac.asm.org/

Issue Date: 2014

pages:5060-5067Identifiers

Urn: uuid:1be6ab4f-8757-4a44-9bc4-55f306597df4

Source identifier: 469493

Eissn: 1098-6596

Doi: https://doi.org/10.1128/aac.02727-13

Issn: 0066-4804 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Animals Mice, Inbred ICR Mice Plasmodium falciparum Sporozoites Malaria, Falciparum Imidazoles Piperazines Antimalarials Inhibitory Concentration 50 Tiny URL: pubs:469493

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Autor: Kuhen, KL - - - Chatterjee, AK - - - Rottmann, M - - - Gagaring, K - - - Borboa, R - - - Buenviaje, J - - - Chen, Z - - - Francek

Fuente: https://ora.ox.ac.uk/objects/uuid:1be6ab4f-8757-4a44-9bc4-55f306597df4



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