Figure 8: In vitro generation of SC81458 and SC83288-resistant P. falciparum clones.
From: SC83288 is a clinical development candidate for the treatment of severe malaria
(a,b) ∼1010 infected erythrocytes were treated with increasing concentration of SC81458 (a) or SC83288 (b) and the decrease in drug susceptibility was monitored over time. Clones obtained at different time points during selection are indicated. The means±s.e.m. of at least three independent determinations are shown. (c) Cross resistance between SC81458- and SC83288-selected clones. (d) Identified single-nucleotide polymorphisms (SNPs) and gene amplifications in the genome of resistant clones. The arrows point in the direction of increased selective pressure. SNPs and gene amplifications associated with resistance to SC compounds are highlighted in blue. This includes PfMDR2 (position 1237), a putative ATP-dependent RNA helicase DBP9 (position 533) and PfATP6 (position 322 and 325), as well as an amplification of the PfATP6 locus.
