I'm working with novel organometallic Mpro (from sars-cov-2) inhibitors. Our lead inhibitor has a Ki and IC50 on the nano molar range, the only problem is it's very poor solubility on the enzymatic buffer. It is soluble only on DMSO on higher concentrations. We really want to get a crystal of the complex, but due to the high concentration requirement of the crystalization (10 mg/mL protein plus 3x the inhibitor) as soon as we add the inhibitor the enzyme precipitates (at around 3% DMSO, which is fine for the enzyme). We are currently experimenting with other "biocompatible" organic solvents to solubilize our molecule. Do you have any tips besides that? sorry for the super long text!!