Figure 6.

Cross-resistance of the spiroindolone resistant parasite line NITD609-R^Dd2-clone#2 to the 11 Na⁺-disrupting Pathogen Box compounds. The IC₅₀ for inhibition of the proliferation of the spiroindolone resistant NITD609-R^Dd2-clone#2 parasite line (which carries two mutations in PfATP4: T418N and P990R) is plotted as a function of the IC₅₀ for inhibition of the proliferation of the parental Dd2 line. The dashed line represents the line onto which compounds for which the two strains have identical IC₅₀ values would fall. Those compounds to which the PfATP4 mutant (NITD609-R^Dd2-clone#2) parasite line is resistant, relative to the parental line, fall above the dashed line. KAE609 is represented by the filled circle. The 11 PfATP4-associated compounds are represented by unfilled circles. The non-PfATP4-associated antimalarials artemisinin and chloroquine are represented by the triangle and square, respectively. The IC₅₀ values for each compound, for both parasite lines, are listed in Table 2.