title: 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.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University.
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Lee
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010744:Phosphoric Monoester Hydrolases