However, compound 10, which is the enantiomer of 9 showed no binding to SmBRD3(1) or SmBRD3 (2), and the corresponding ethyl ester, 17, did not have substantial effects on either phenotype or motility. This result suggests a link between the phenotypic effects and inhibition of SmBRD3( ) function. In contrast, of the SmBRD3(1) binding compounds evaluated (orange, Figure ), only (+)-JQ1 (2) showed activity ex vivo, which is in line with previous reports. The phenotype and movement EC50 values of the more active compounds, 18 and 20-22 are in the low micromolar range (Table ), but there is only moderate correlation with the SmBRD3( ) Kd values of the corresponding carboxylic acids. This reflects the range of characteristics that affect the activity of these compounds on the live schistosomula, including permeability and metabolic stability. The effect of compound treatment on worm pairing, with 1 and 0 corresponding to 100% and 0% of parasite pairs following 72 h drug-treatment, respectively, (mean of n = 2 compound screens). The ex vivo screens of these small molecules on adult schistosome pairs broadly mirrors the results of the phenotypic and motility assays performed on schistosomula, with the ethyl esters of the I-BET726 derivatives again showing the greatest effects on the adult worms. The benzothiophene (16), benzofuran (18), indole (20), benzothiazole (21) and quinoline (22) derivatives all showed substantial effects on worm movement (Figure ); however, none of the compounds were lethal to the parasite. Compounds that affect worm motility are also associated with reduced oviposition (Figure ) and decreased worm pairing (Figure ). It is notable that compound 10 does not bind to SmBRD3( ), but its ethyl ester (17) showed some modest effects on worm movement and egg count (Figure and), but not on worm pairing (Figure ).