Assessing the effects of SmBRD3( ) ligands on schistosomula A high-throughput imaging platform that quantifies both phenotype and motility ex vivo, was used to screen compounds against schistosomula; their effects were assessed as previously described. Briefly, the schistosomula stage of S. mansoni was obtained by mechanical transformation of cercariae, dispensed into 384-well tissue culture plates, and dosed with 20 µM (Figure ) or 10 µM (Figure ) of each compound. Following 72 h co-incubation of the schistosomula and compound, the plate was subjected to high content imaging to quantify the effects of each compound. As expected, no carboxylic acid-containing I-BET726 analogues showed substantial activity on schistosomula phenotype and motility metrics, which we attributed to low permeability resulting from higher polarity (determined by chromLogD, see above). However, the majority of their ethyl ester derivatives were classified as hits. The quinoline derivative 22, and the benzothiazole derivative 21, showed the greatest effects on schistosomula phenotype and motility, while the benzofuran derivative 18 also had substantial effects on motility (Figure and Figure ). The carboxylic acid counterparts of these compounds all have affinity for SmBRD3 (2).