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. Author manuscript; available in PMC: 2017 Jul 18.
Published in final edited form as: Nature. 2016 Sep 7;538(7625):344–349. doi: 10.1038/nature19804

Figure 1. Cascading triage strategy reveals targets for some of the hit compounds and highlights potential novel mechanisms of action for others.

Figure 1

a–e, A total of 468 compounds (‘positives’ in the growth inhibition primary assay) were tested in dose against P. falciparum Dd2, a transgenic P. falciparum line expressing Saccharomyces cerevisiae DHODH (PfscDHODH), a P. falciparum strain resistant to NITD609 (Pf NITD609R) and a mammalian cell line (HepG2). P. falciparum ATPase4 is the presumed molecular target of NITD609 (ref. 9). a, Compounds were clustered across the horizontal axis by structural similarity. Colours represent compound potency (EC50). Two compound clusters, exemplified by BRD0026 (b) and BRD7539 (c), showed selectively reduced potency against the Pf NITD609R and PfscDHODH strains, respectively, while BRD73842 (d) and BRD3444 (e) were equipotent across the three P. falciparum strains. Pb, P. berghei; Pf, P. falciparum; Pv, P, vivax; PheRS, phenylalanyl-tRNA synthetase.