TABLE 2.

In vitro resistance mechanism of KAF156^a

Selection agent	Culture	SNP(s)b	Mean IC50 (nM) ± SD
			GNF707	GNF452	KAF156
DMSO		None (Dd2, WT)	8.1 ± 0.9	7.6 ± 2.0	1.8 ± 0.6
GNF707	1R	V1254F	170	49	2.0
	2R	L830V	150	61	2.0
	3R	E834D	1,300	360	36
GNF452	1R	M1069I, L830V	3,600	1,200	97
	3R	S1076I, L830V	2,600	7,300	3,600
KAF156	1AR	Q821H, S1076R	5,300	1,900	10
	1BR	P822T, S1076R	>10,000	>10,000	73
	2BR	S1076I	3,000	>10,000	1,600
	3AR	E834D	6,900	1,800	24
	3BR	E834D	5,000	1,600	16

^aFive independent cultures of P. falciparum strain Dd2 were cultured in the presence of increasing concentrations of KAF156 over 4 months and, in a similar manner, three independent cultures were pressured with GNF707, and two independent cultures were pressured with GNF452. Parasitemia was monitored daily, and the compound concentration was increased 2-fold when the parasitemia reached ≥3%. For each of the resistant strains, the SNPs detected and the antimalarial activities (IC₅₀) are as indicated for KAF156, GNF707, and GNF452. Data are presented to two significant figures as the median value from two to four independent experiments; the IC₅₀s were consistent within 1.5-fold across experiments.

^bSNPs, single-nucleotide polymorphisms. SNPs were confirmed by capillary sequencing of pfcarl (PFC0970w).