Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
ACS Chem Biol
2012 Jan 20;71:185-96. doi: 10.1021/cb200305u.
Show Gene links
Show Anatomy links
Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.
Kwiatkowski N
,
Deng X
,
Wang J
,
Tan L
,
Villa F
,
Santaguida S
,
Huang HC
,
Mitchison T
,
Musacchio A
,
Gray N
.
???displayArticle.abstract???
The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions.
Abe,
LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis.
2006, Pubmed
Abe,
LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis.
2006,
Pubmed
Aliagas-Martin,
A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B.
2009,
Pubmed
Bayliss,
Structural basis of Aurora-A activation by TPX2 at the mitotic spindle.
2003,
Pubmed
,
Xenbase
Bird,
Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A.
2008,
Pubmed
Bishop,
Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity.
2002,
Pubmed
Bolton,
Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation.
2002,
Pubmed
,
Xenbase
Cheeseman,
Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p.
2002,
Pubmed
Chen,
Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells.
2003,
Pubmed
Deng,
Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2.
2011,
Pubmed
Deng,
Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a Potent and Selective Inhibitor of Big MAP Kinase 1.
2011,
Pubmed
Eyers,
A novel mechanism for activation of the protein kinase Aurora A.
2003,
Pubmed
,
Xenbase
Fabian,
A small molecule-kinase interaction map for clinical kinase inhibitors.
2005,
Pubmed
George,
Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth.
2009,
Pubmed
Giet,
Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules.
2002,
Pubmed
,
Xenbase
Girdler,
Molecular basis of drug resistance in aurora kinases.
2008,
Pubmed
Glover,
Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles.
1995,
Pubmed
Hannak,
Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans.
2001,
Pubmed
Harrington,
VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo.
2004,
Pubmed
Hirota,
Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells.
2003,
Pubmed
,
Xenbase
Honda,
Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis.
2003,
Pubmed
Huang,
Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly.
2009,
Pubmed
Hutterer,
Mitotic activation of the kinase Aurora-A requires its binding partner Bora.
2006,
Pubmed
Jelluma,
Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment.
2008,
Pubmed
Jeyaprakash,
Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together.
2007,
Pubmed
Kelly,
Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly.
2007,
Pubmed
,
Xenbase
Kimura,
Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1.
1997,
Pubmed
,
Xenbase
Koffa,
HURP is part of a Ran-dependent complex involved in spindle formation.
2006,
Pubmed
,
Xenbase
Kufer,
Human TPX2 is required for targeting Aurora-A kinase to the spindle.
2002,
Pubmed
,
Xenbase
Kwiatkowski,
Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.
2010,
Pubmed
Lampson,
Correcting improper chromosome-spindle attachments during cell division.
2004,
Pubmed
Lénárt,
The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1.
2007,
Pubmed
Manfredi,
Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase.
2007,
Pubmed
Mori,
NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment.
2007,
Pubmed
Mortlock,
Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase.
2007,
Pubmed
Patricelli,
Functional interrogation of the kinome using nucleotide acyl phosphates.
2007,
Pubmed
Rieder,
Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint.
2004,
Pubmed
Santaguida,
Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction.
2011,
Pubmed
Santaguida,
Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine.
2010,
Pubmed
Saurin,
Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis.
2011,
Pubmed
Sessa,
Mechanism of Aurora B activation by INCENP and inhibition by hesperadin.
2005,
Pubmed
,
Xenbase
Shi,
Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5.
2008,
Pubmed
Tan,
Navitoclax enhances the efficacy of taxanes in non-small cell lung cancer models.
2011,
Pubmed
Tanaka,
Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections.
2002,
Pubmed
Terada,
AIM-1: a mammalian midbody-associated protein required for cytokinesis.
1998,
Pubmed
Toji,
The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase.
2004,
Pubmed
Tsai,
A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly.
2003,
Pubmed
,
Xenbase
Vader,
Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody.
2006,
Pubmed
Wertz,
Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7.
2011,
Pubmed
Yasui,
Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis.
2004,
Pubmed
