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lüll Identification of two potential glycogen synthase kinase 3beta inhibitors for the treatment of osteosarcoma Lu K; Wang X; Chen Y; Liang D; Luo H; Long L; Hu Z; Bao JActa Biochim Biophys Sin (Shanghai) 2018[May]; 50 (5): 456-464Osteosarcoma is the most common primary malignant bone tumor among adolescents worldwide with high mortality rate. Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase and is considered as a validated target in osteosarcoma therapy. Therefore, the study of GSK3beta inhibitors is one of the most popular fields in anti-osteosarcoma drug development. Here, the tools of bioinformatics were used to screen novel effective inhibitors of GSK3beta from ZINC Drug Database. The molecular docking, molecular dynamic simulations, MM/GBSA, and energy decomposition analysis were performed to identify the inhibitors. Finally, ZINC08383479 and ZINC08441251 were selected as potential GSK3beta inhibitors. These two inhibitors were evaluated by GSK3beta kinase inhibition assay in vitro. The inhibition of cell proliferation was tested in osteosarcoma cell lines U2OS and MG63 in vitro. The result showed that ZINC08383479 and ZINC08441251 had high inhibition activity against GSK3beta. We found that CHIR99021 (a known GSK3beta inhibitor), ZINC08383479, and ZINC08441251 had significant inhibition activity in U2OS cells and MG63 cells. These findings may provide new ideas for the design of more potent GSK3beta inhibitors and therapeutic targets for osteosarcoma.|*Molecular Docking Simulation[MESH]|Binding Sites[MESH]|Bone Neoplasms/enzymology/pathology[MESH]|Cell Line, Tumor[MESH]|Cell Proliferation/*drug effects[MESH]|Glycogen Synthase Kinase 3 beta/*antagonists & inhibitors/chemistry/metabolism[MESH]|Humans[MESH]|Hydrogen Bonding[MESH]|Molecular Dynamics Simulation[MESH]|Molecular Structure[MESH]|Osteosarcoma/enzymology/pathology[MESH]|Protein Binding[MESH]|Protein Domains[MESH]|Protein Kinase Inhibitors/chemistry/metabolism/*pharmacology[MESH] |