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Previously, we identified the plasmodial lactate transporter, PfFNT, a member of the microbial formate\u2013nitrite transporter family, as a novel antimalarial drug target. With the pentafluoro\u20103\u2010hydroxy\u2010pent\u20102\u2010en\u20101\u2010ones, we discovered PfFNT inhibitors that potently kill <jats:italic>P. falciparum<\/jats:italic> parasites <jats:italic>in\u2005vitro<\/jats:italic>. Four additional human\u2010pathogenic <jats:italic>Plasmodium<\/jats:italic> species require attention, that is, <jats:italic>P. vivax<\/jats:italic>, most prevalent outside of Africa, and the regional <jats:italic>P. malariae<\/jats:italic>, <jats:italic>P. ovale<\/jats:italic> and <jats:italic>P. knowlesi<\/jats:italic>. Herein, we show that the plasmodial FNT variants are highly similar in terms of protein sequence and functionality. The FNTs from all human\u2010pathogenic plasmodia and the rodent malaria parasite were efficiently inhibited by pentafluoro\u20103\u2010hydroxy\u2010pent\u20102\u2010en\u20101\u2010ones. We further established a phenotypic yeast\u2010based FNT inhibitor screen, and found very low compound cytotoxicity and monocarboxylate transporter 1 off\u2010target activity on human cells, particularly of the most potent FNT inhibitor BH267.meta, allowing these compounds to proceed towards animal model malaria studies.<\/jats:p>","DOI":"10.1002\/cmdc.202000952","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:41:34Z","timestamp":1608291694000},"page":"1283-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pentafluoro\u20103\u2010hydroxy\u2010pent\u20102\u2010en\u20101\u2010ones Potently Inhibit FNT\u2010Type Lactate Transporters from all Five Human\u2010Pathogenic <i>Plasmodium<\/i> Species"],"prefix":"10.1002","volume":"16","author":[{"given":"Philipp","family":"Walloch","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry 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