Abstract
Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 Å cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.
| Original language | English |
|---|---|
| Pages (from-to) | 180-192 |
| Number of pages | 13 |
| Journal | ACS Chemical Biology |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 20 2008 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
Cite this
Discovery of selective aminothiazole aurora kinase inhibitors. / Andersen, Carsten B.; Wan, Yongqin; Chang, Jae W.; Riggs, Blake; Lee, Christian; Liu, Yi; Sessa, Fabio; Villa, Fabrizio; Kwiatkowski, Nicholas; Suzuki, Melissa; Nallan, Laxman; Heald, Rebecca; Musacchio, Andrea; Gray, Nathanael S.
In: ACS Chemical Biology, Vol. 3, No. 3, 20.03.2008, p. 180-192.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Discovery of selective aminothiazole aurora kinase inhibitors
AU - Andersen, Carsten B.
AU - Wan, Yongqin
AU - Chang, Jae W.
AU - Riggs, Blake
AU - Lee, Christian
AU - Liu, Yi
AU - Sessa, Fabio
AU - Villa, Fabrizio
AU - Kwiatkowski, Nicholas
AU - Suzuki, Melissa
AU - Nallan, Laxman
AU - Heald, Rebecca
AU - Musacchio, Andrea
AU - Gray, Nathanael S.
PY - 2008/3/20
Y1 - 2008/3/20
N2 - Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 Å cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.
AB - Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 Å cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.
UR - http://www.scopus.com/inward/record.url?scp=42449137119&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42449137119&partnerID=8YFLogxK
U2 - 10.1021/cb700200w
DO - 10.1021/cb700200w
M3 - Article
C2 - 18307303
AN - SCOPUS:42449137119
VL - 3
SP - 180
EP - 192
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 3
ER -