Virtual screening with docking simulations and biochemical evaluation of VHY phosphatase inhibitors

Abstract

Although VH1-related member Y (VHY) phosphatase is responsible for the pathogenesis of neuroinflammatory diseases, no small-molecule inhibitor of VHY has been reported so far. Here we first report eight VHY inhibitors identified from molecular docking-based virtual screening and subsequent enzyme inhibition assays. These inhibitors exhibit good biochemical potencies against VHY, with associated IC50 values ranging from 1 to 9 μm. Because all these inhibitors were also screened in silico for having desirable physicochemical properties as a drug candidate, they deserve further investigation by structure-activity relationship studies to develop new medicines for the treatment of neuroinflammatory diseases. The structural features of VHY-inhibitor interactions relevant to the micromolar-level inhibitory activity are addressed in detail.