Fig. 2. Primary screening of the PRB for hits against P. falciparum parasites.

a Supra-hexagonal maps of all 400 compounds included in the PRB after analysis on P. falciparum NF54 asexual blood stage parasites, stage IV/V gametocytes, and Pb liver stage. Each hexagon is indicative of a single compound and the order of the hexagon is the same between the plots. Colours on the heat bar indicate percentage of inhibition of proliferation (asexual blood stage parasites) or viability (stage IV/V gametocytes) after treatment with each compound at either 2 µM (asexual blood stages) or 5 µM (stage IV/V gametocytes or liver stages), screened at least in duplicate. The data for the stage IV/V gametocytes are compiled from hits identified with three different assay platforms, run in parallel (ATP, PrestoBlue^® and luciferase reporter expression) with any hit on any platform included, and where identified on >2 platforms, the highest value was included. b Proportional distribution of hits (>50% inhibition @ 2 µM for asexual blood stages or 5 µM for stage IV/V gametocytes and liver stages) based on disease area as defined in the PRB. Bars are delineated to show activity distribution. ABS asexual blood stages, GC stage IV/V gametocytes, L liver stage. c Stratification of hits from a (>50% inhibition @ 2 µM for asexual blood stages or 5 µM for stage IV/V gametocytes and liver stages, screened in duplicate). The number of compounds that could be associated with a specific biological activity or target indicator is shown. Protein targets/metabolic pathways were identified based on the descriptions of compounds with known activity in the PRB in other disease systems. FT farnesyltransferase inhibitors, GPCR G protein-coupled receptors, S1P sphingosine-1-phosphate receptor modulators, CYP cytochrome inhibitors, ETC electron transport chain, DHFR dihydrofolate reductase, DHODH dihydroorotate dehydrogenase.