Kelli L. KuhenArnab K. ChatterjeeMatthias RottmannKerstin GagaringRachel BorboaJennifer BuenviajeZhong ChenCarolyn FrancekTao WuAdvait NagleS. Whitney BarnesDavid PlouffeMarcus C.S. LeeDavid A. FidockWouter GraumansMarga Van De Vegte-BolmerGeert J. Van GemertGrennady WirjanataBoni SebayangJutta MarfurtBruce RussellRossarin SuwanaruskRic N. PriceFrancois NostenAnchalee TungtaengMontip GettayacaminJetsumon SattabongkotJennifer TaylorJohn R. WalkerDavid TullyKailash P. PatraErika L. FlanneryJoseph M. VinetzLaurent ReniaRobert W. SauerweinElizabeth A. WinzelerRichard J. GlynneThierry T. DiaganaThe Genomics Institute of the Novartis Research FoundationSwiss Tropical and Public Health Institute (Swiss TPH)Universitat BaselColumbia University, College of Physicians and SurgeonsRadboud University Nijmegen Medical CentreMenzies School of Health ResearchEijkman Institute for Molecular BiologyAgency for Science, Technology and Research, SingaporeShoklo Malaria Research UnitMahidol UniversityNuffield Department of Clinical MedicineArmed Forces Research Institute of Medical Sciences, ThailandUniversity of California, San DiegoUniversity of California, San Diego, School of MedicineNovartis Institute for Tropical Diseases Pte. Ltd.California Institute for Biomedical Research2018-11-092018-11-092014-01-01Antimicrobial Agents and Chemotherapy. Vol.58, No.9 (2014), 5060-506710986596006648042-s2.0-84906079854https://repository.li.mahidol.ac.th/handle/20.500.14594/34878Renewed 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. Copyright © 2014 Kuhen et al.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.02727-13