Characterization of a highly selective inhibitor of the Aurora kinases. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Ferguson, Fleur M.; Doctor, Zainab M.; Chaikuad, Apirat; Sim, Taebo; Kim, Nam Doo; Knapp, Stefan; Gray, Nathanael S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4405
• Page End: 4408
• Publication Date: 2017-09-15
• Subjects: PLK4 Polo-like kinase 4 -- FACS fluorescence activated cell sorting -- DMSO dimethylsulfoxide -- AML acute myeloid leukemia -- T-ALL T-cell acute lymphoblastic leukemia -- ABL1 Abelson Tyrosine-Protein Kinase 1 -- LRRK2 Leucine Rich Repeat Kinase 2 -- BRD4 Bromodomain-Containing Protein 4 -- ERK5 Mitogen-activated protein kinase 7 -- LC-MS/MS Liquid Chromatography–Mass Spectrometry/Mass Spectrometry; Aurora kinase -- Selective kinase inhibitor -- Pan-Aurora inhibitor -- Mitosis -- Cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.08.016
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.