Aurora B kinazı hedef alan özgün küçük molekül inhibitorlerin saptanması

Cell division is a complex process which is regulated by several checkpoints and feedback mechanisms. Aurora B is a mitotic checkpoint kinase having essential roles during cell division. It is involved in proper chromosome alignment and attachment of mitotic spindle to centromeres. It localizes microtubules near kinetochores during mitosis in connection with CPC (chromosome passenger complex). That complex consists of INCENP (inner centromere protein), Borealin and Survivin proteins all of which are phosphorylation targets of Aurora B. Kinase activity and complex binding of Aurora B is increased after interacting with CPC partners, especially INCENP. Abnormal expression patterns of Aurora B are shown to result in chromosome instability and aneuploidy followed by tumorigenesis. And yet, Aurora B over-expression is observed in a large number of cancers. Previous studies have revealed that inhibiton of Aurora B induced G2/M arrest or apoptosis in cancer cells making it a novel therapeutic target for cancer treatment. There are several Aurora kinase inhibitors, some of which are under clinical trial. However all of those inhibitors target kinase domain. In this study we aimed to characterize novel potential inhibitors that target Aurora B kinase via different molecular mechanisms.