title: Identification of 3,5,6-substituted indolin-2-one's inhibitors of Aurora B by development of a luminescent kinase assay.
abstract: Aurora B kinase plays an important role in the cell normal mitosis and overexpresses in a variety of tumors. Inhibition of Aurora B kinase resulted in an apoptosis of cancer cells, which prevented tumor growth in xenograft models. In this Letter, we developed a luminescent kinase assay to perform high-throughput screening for identification of small molecule Aurora B inhibitors. Two 3,5,6-substituted indolin-2-one derivatives were identified within an in-house compound library. Their new derivatives were then designed and synthesized that resulting two new inhibitors of Aurora B kinase with improved potency. Docking simulation further demonstrated the proposed binding modes between indolin-2-one inhibitor and Aurora B.
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xilei
authors.initials: X
authors.lastname: Xie
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Tsinghua-Peking Center for Life Sciences, China; Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Haidian Dist., Beijing 100084, China. Electronic address: gangliu27@yahoo.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057075:Enzyme Assays / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008163:Luminescent Measurements / Q000379:methods; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D007211:Indoles; D010455:Peptides; D047428:Protein Kinase Inhibitors; C456900:indolin-2-one; D064107:Aurora Kinase B
keywords: Aurora B; Indolin-2-one; Luminescent kinase assay; Small molecule inhibitor