Fig. 6. IC₅₀ and phenotypic effect of human kinase inhibitors on Plasmodium blood-stage development.

a IC₅₀ values of the human kinase inhibitors Crizotinib (MET/ALK inhibitor), PHA-665752 (Met inhibitor), SB-590885 (B-Raf inhibitor) and Sorafenib (B-Raf inhibitor, P. falciparum only) on asynchronous P. falciparum and ring-stage P. knowlesi asexual growth. b Growth inhibition curve for asynchronous P. falciparum, IC₅₀ measured after 72 h of compound exposure, n = 3, n = 2 for sorafenib (n represents biologically independent samples), data are presented as mean values ± SEM. c Growth inhibition curve for P. knowlesi, IC₅₀s measured after 50 h of compound exposure, n = 3 biologically independent samples, data are presented as mean values ± SEM. d Effect of treatment with 5× the IC₅₀ value of the compounds Crizotinib, PHA-665752, SB-590885, Artemisinin, DMSO (equivalent volume of DMSO in Crizotinib sample) and heparin (15 μl/ml) on highly synchronous (4 h window) P. falciparum cultures over 88 h (n = 5 biologically independent samples). The Y-axis represents the live parasitemia values for each time point normalized to a starting total parasitemia of 2%, data are presented as mean values ± SEM. e Effect of treating mice with PHA-665752 on the growth of P. berghei. The graph shows relative luminescence units (RLU) in the blood of BALB/c mice infected with parasites constitutively expressing firefly luciferase and treated or not with PHA-665752 at 25 mg/kg at times indicated by arrows. *p < 0.01 by two-tailed T-test; n = 7 mice per treatment group, data are presented as mean values ± SEM. Source data are provided as a Source Data file.