title: A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting Aurora B kinase activity.
abstract: Aurora kinases play a key role in the regulation of mitosis and have been regarded as promising targets of cancer therapy. In this paper we describe a thienopyrimidine derivative (S7), a novel potent ATP-competitive hit inhibitor of Aurora B kinase screened through a HTS system, with the IC50 141.12 nM in the biochemical kinase activity assay. Human tumor cells treated with S7 showed dose-dependent inhibition of auto-phosphorylation of Aurora B on Thr232 and another widely-used marker specific for Aurora B kinase, the phosphorylation of Histone H3 (Ser 10), demonstrating endogenous Aurora B kinase activity were inhibited at cellular level. Moreover, S7 treatment induced proliferation inhibition, colony formation inhibition and apoptosis of human tumor cell lines in a dose- and time-dependent manner.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Hairong
authors.initials: H
authors.lastname: Hu
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Lang
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C476003:thienopyrimidine; D064107:Aurora Kinase B
keywords: 2-(5-phenylthieno [2,3-d] pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline; ATP-competitive; Apoptosis; Aurora B; Growth inhibition; HTS; IC(50); Molecular modeling; PhAurB (Thr232); PhH3 (Ser 10); S7; Small-molecule inhibitor; high throughput screening; inhibitory concentration (50%); phospho-Aurora B (Thr232); phospho-histone H3 (Ser 10)