title: Identification of novel polo-like kinase 1 inhibitors by a hybrid virtual screening.
abstract: Polo-like kinase 1 is an important and attractive oncological target that plays a key role in mitosis and cytokinesis. A combined pharmacophore- and docking-based virtual screening was performed to identify novel polo-like kinase 1 inhibitors. A total of 34 hit compounds were selected and tested in vitro, and some compounds showed inhibition of polo-like kinase 1 and human tumor cell growth. The most potent compound (66) inhibited polo-like kinase 1 with an IC(50) value of 6.99 μm. The docked binding models of two hit compounds were discussed in detail. These compounds contained novel chemical scaffolds and may be used as foundations for the development of novel classes of polo-like kinase 1 inhibitors.
authors.affiliation: Laboratory of Molecular Design and Drug Discovery, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Lu
authors.forename: Shan-Liang
authors.initials: SL
authors.lastname: Sun
authors.forename: Hai-Chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Chen
authors.forename: Hao-Liang
authors.initials: HL
authors.lastname: Yuan
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Gao
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1