Compounds produced in medicinal chemistry efforts often have low aqueous solubility when compared to biological ligands. When poor compound solubility is suspected, one may try dimethylsulfoxide (DMSO) to solubilize the compound. Dissolve the compound in 100% DMSO and THEN dilute to a lower DMSO concentration. Dissolving a compound in dilute DMSO can be a very slow kinetic process.
One may consider evaluating other solvents for compound solubility, including Polyethylene glycol 200, ethylene glycol, 2-propanol, or methanol.
Another option is to evaluate adding the dry compound to the drop as has been done successfully with numerous insoluble heavy atom derivatives. Although the compound may not appear to be soluble in the drop, there may be some solubility, sufficient for the compound to bind the protein.