Establishment Molecule-based Models For Aurora B Kinase Inhibitors Screening

Kinases including Serine/Threoine kinases and protein tyrosine kinases, are important regulators of intracellular signal-transduction pathways mediating cell proliferation, differentiation and migration. Deregulation of kinases expression results in enhanced kinase activity and tumorigenesis.Aurora-B kinase is a chromosomal passenger protein which is localized to centromeres in metaphase and stays associated with the spindle midzone in anaphase. Aurora-B regulates critical steps throughout mitosis:upon entry into mitosis Aurora-B phosphorylates histone H3 on position serinelO followed by the control of correct biorientation and segregation of the chromosomes in metaphase, where it functions as a gatekeeper for the spindle assembly checkpoint. The Aurora-B kinase, however, has also been shown to be strongly expressed in many tumor types compared with essentially nonproliferating matched normal tissue, with expression levels often correlating with disease characteristics or outcome.In this study, we established convenient and effective ELISA-based Aurora B screening model for high-throughput Aurora B Kinase Inhibitors Screening. Briefly, the Aurora B was expressed using the baculovirus system. Then a high-throughput, 96-well format ELISA assay were established to screen for novel Aurora B inhibitors. With the availability of this platform,182 compounds were screened,5 active compounds were obtained. Among them,2 compounds could inhibit the autophosphorylation of the Aurora B kinase in MCF7 cell line.