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This compound was also effective against\n                  <jats:italic>P. knowlesi<\/jats:italic>\n                  and\n                  <jats:italic>P. cynomolgi<\/jats:italic>\n                  . In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  revealed that a mutation in\n                  <jats:italic>PfSec13<\/jats:italic>\n                  , which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  , its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Editor\u2019s Summary<\/jats:title>\n                  <jats:p>\n                    Here we report the mode of action and mechanism of resistance of a pan-antimalarial agent, MED6-189, which disrupts apicoplast function and vesicular trafficking in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    .\n                  <\/jats:p>\n                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