Discovery of covalent inhibitors for MIF tautomerase via cocrystal structures with phantom hits from virtual screening

Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.

Graphical abstractVirtual screen hits were shown to be covalent inhibitors by biochemical and X-ray crystallographic studies.Figure optionsDownload full-size imageDownload as PowerPoint slide