镇学初教授在J Med Chem上发表论文Discovery of novel inhibitors targeting the macrophage migration inhibitory factor via structure-based virtual screening and bioassays.
immune responses and is regarded as an attractive antiinflammatory pharmacological target. In this study, molecular
docking-based virtual screening and in vitro bioassays were utilized to identify novel small-molecule inhibitors of MIF. The
in vitro enzyme-based assay identified that ten chemically diverse compounds exhibited potent inhibitory activity against
MIF in the micromolar regime, including three compounds with IC50 values below 10 μM and one with an IC50 value below 1 μM (0.55 μM); the latter is 26-fold more potent than the reference compound ISO-1. The structural analysis demonstrates that most of these active compounds possess novel structural scaffolds. Further in vitro cell-based glucocorticoid overriding, chemotaxis, and Western blotting assays revealed that the three compounds can effectively inhibit the biological functions of MIF in vitro, suggesting that these compounds could be potential agents for treating inflammatory diseases.
