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. 2023 May 18;30(5):470–485.e6. doi: 10.1016/j.chembiol.2023.03.002

Table 2.

P. falciparum asexual blood-stage minimal inoculum for resistance (MIR) selection summary

Name Chemical class Starting selective pressure Resistant parasites in 4 wells of 2.5 × 106 Resistant parasites in 3 wells of 3 × 107 Resistant parasites in 3 flasks of 3 × 108 MIR Selected proteasome mutation IC50 fold shift against selection compound
WLL vinyl sulfone 3 × IC50 (50.4 nM) none none none >1 × 109 N/A N/A
J-71 epoxyketone 3 × IC50 (152.4 nM) none 1/3 wells N/D 1 × 108 β5 A50V 3.1×
J-80 epoxyketone 3 × IC50 (88.2 nM) none none 3/3 flasks 3 × 108 β5 M45R, β5 M45V 35.1×, 11.6×
TDI-8304 macrocyclic peptide 3 × IC50 (33 nM) none 3/3 wells N/D 3 × 107 β6 S157L, β6 N151Y 2,621×, 1.7×

IC50 fold shifts were calculated as the ratio of the IC50 of a compound against the selected mutant over its IC50 against the Dd2-B2 parental line. N, n = 3–20, 2. N/D, not done; N/A, not applicable. MIRs were calculated as the total number of parasites inoculated divided by the total number of positive cultures (when obtained). The formula extends up to the largest inoculum at which parasites were obtained (or tested in the case of negative cultures), and includes lower inocula (see STAR Methods).