Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Pantothenamide stability.
  • Fig. S2. Parasite life cycle.
  • Fig. S3. Pantothenate competition assays.
  • Fig. S4. PANK activity.
  • Fig. S5. Expression of PfPANK1.
  • Fig. S6. Cellular pantothenamide metabolism and targeted metabolomics.
  • Fig. S7. Pantothenate and pantothenamide metabolism in saponin-isolated parasites versus uninfected red blood cells.
  • Fig. S8. Erythrocytes preexposed to MMV689258 are less susceptible to malaria infection.
  • Fig. S9. Drug-resistant parasite (ACS-T627A and ACS11-E660K) transmission to mosquitoes.
  • Fig. S10. Pantothenamide-resistant parasites (ACS-T627A and ACS11-E660K) have reduced fitness.
  • Fig. S11. Sequence verification of CRISPR-Cas9–engineered mutations.
  • Fig. S12. Metabolomics of wild-type versus drug-resistant parasites.
  • Fig. S13. Pharmacokinetics of MMV689258 in rodents.
  • Fig. S14. Dose-normalized plasma exposure of MMV689258 in NODscidIL2Rγnull mice.
  • Fig. S15. Red blood cell counts in PfSCID mice treated with MMV689258.
  • Fig. S16. Cell-type specificity and primary human hepatocyte metabolomics.
  • Table S1. Selection of compounds to illustrate structure-activity relationship.
  • Table S2. IC50 values of compounds shown in Fig. 1.
  • Table S3. Description of strains used in resistance panel.
  • Table S4. Targeted metabolomics values for select compounds of interest.
  • Table S5. Pharmacokinetic parameters derived from the data shown in fig. S13.
  • Table S6. Renal excretion of MMV689258 in rats.
  • Table S7. Biliary excretion of MMV689258 in rats.
  • Table S8. In vitro ADME parameters of MMV689258.
  • Table S9. Primers used for genetic studies.

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Other Supplementary Material for this manuscript includes the following:

  • Table S10 (Microsoft Excel format). Source data for Figs. 1C, 2 (A to E), 3C, 4B, and 5 (A to C).