As smbrd3 is most abundantly expressed in miracidia and sporocysts (Figure ), we were intrigued to investigate whether our SmBRD3 BRD ligands affect ex vivo miracidia-to-sporocyst transformation. This process occurs naturally in the intermediate host snail and is critical for lifecycle progression. Two SmBRD3(2) ligand pro-drugs compounds 22 and 16, showed concentration dependent inhibition of the miracidia to sporocyst transformation (Figure and Figure ). Interestingly, compound 22 is the ethyl ester of compound 15, which has the highest affinity for SmBRD3(2) (Table ). Most other SmBRD3(2) ligands had no effect on the transformation. The negative control, 34, and (+)-JQ1 were toxic at the higher concentrations (Figure ). While OXFBD02 and OXFBD04 showed modest effects on the miracidia to sporocyst transformation at a concentration of 25 μM, the other SmBRD3(1) selective ligands generally had no effect in this assay (Figure ). Determining the permeability of acids and ethyl esters in adult worms