title: A small molecule identified through an in silico screen inhibits Aurora B-INCENP interaction.
abstract: Aurora B is a serine/threonine kinase that has a central role in the regulation of mitosis. The observation of Aurora B overexpression in cancer makes it a promising target to develop antitumoral inhibitors. We describe a new potential inhibitor that exclusively targets the interaction site of Aurora B and its activator INCENP. We performed a structure-based virtual screening and determined five potential candidates of 200 000 compounds, which selectively bind to the Aurora B::INCENP interaction site, but not to the ATP-binding site (kinase pocket) of Aurora B or other related kinases. Further characterization in vivo validated the inhibitory role of one of these five compounds in Aurora B::INCENP complex formation and exhibited hallmarks of Aurora inhibition such as chromosome congression and segregation defects that interfere with the progression into cytokinesis and result in multinuclear cells. Our results provide an alternative approach on the way of exploring specific kinase inhibitors.
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Unsal
authors.affiliation: Department of Chemical and Biological Engineering, Koç University, Istanbul, Turkey.
authors.forename: Bahar
authors.initials: B
authors.lastname: Degirmenci
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey.
authors.forename: Büşra
authors.initials: B
authors.lastname: Harmanda
authors.affiliation: Department of Chemical and Biological Engineering, Koç University, Istanbul, Turkey.
authors.forename: Burak
authors.initials: B
authors.lastname: Erman
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey. nozlu@ku.edu.tr.
authors.forename: Nurhan
authors.initials: N
authors.lastname: Ozlu
mesh_terms: D064107:Aurora Kinase B / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D048749:Cytokinesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D064107:Aurora Kinase B
keywords: Aurora B kinase; selective kinase inhibitor; structure-based virtual screening