title: Identification of potent VHZ phosphatase inhibitors with structure-based virtual screening.
abstract: VH1-like phosphatase Z (VHZ) has proved to be a promising target for the development of therapeutics for the treatment of human cancers. Here, we report the first example for a successful application of structure-based virtual screening to identify the novel small-molecule inhibitors of VHZ. These inhibitors revealed high potencies with the associated IC(50) values ranging from 3 to 20 µM and were also screened for having desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize inhibitory and anticancer activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of VHZ are discussed in detail.
authors.affiliation: Sejong University, Seoul, Korea. hspark@sejong.ac.kr
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: So Ya
authors.initials: SY
authors.lastname: Park
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Oh
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D015195:Drug Design; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; C497817:DUSP23 protein, human; D054637:Dual-Specificity Phosphatases