Discovery of a Potent, Selective, and Orally Bioavailable Pyridinyl-Pyrimidine Phthalazine Aurora Kinase Inhibitor

2010 ◽  
Vol 53 (17) ◽  
pp. 6368-6377 ◽  
Author(s):  
Victor J. Cee ◽  
Laurie B. Schenkel ◽  
Brian L. Hodous ◽  
Holly L. Deak ◽  
Hanh N. Nguyen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
Orally Bioavailable

scholarly journals PF-03814735, an Orally Bioavailable Small Molecule Aurora Kinase Inhibitor for Cancer Therapy

2010 ◽  
Vol 9 (4) ◽  
pp. 883-894 ◽  
Author(s):  
Jitesh P. Jani ◽  
Joel Arcari ◽  
Vincent Bernardo ◽  
Samit K. Bhattacharya ◽  
David Briere ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
Orally Bioavailable

scholarly journals The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing

2013 ◽  
Vol 62 ◽  
pp. 777-784 ◽  
Author(s):  
Stefan O. Ochiana ◽  
Vidya Pandarinath ◽  
Zhouxi Wang ◽  
Rishika Kapoor ◽  
Mary Jo Ondrechen ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Lead Compound ◽  
Aurora Kinase Inhibitor ◽  
Target Repurposing

A phase l study of three different dosing schedules of the oral aurora kinase inhibitor MSC1992371A in patients with solid tumors

2013 ◽  
Vol 9 (3) ◽  
pp. 215-224 ◽  
Author(s):  
M. Mita ◽  
M. Gordon ◽  
N. Rejeb ◽  
A. Gianella-Borradori ◽  
V. Jego ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor

scholarly journals Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1498-1505 ◽  
Author(s):  
Jürgen den Hollander ◽  
Sara Rimpi ◽  
Joanne R. Doherty ◽  
Martina Rudelius ◽  
Andreas Buck ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Cell Cycle Regulators ◽  
Aurora Kinase Inhibitor ◽  
Aurora Kinases ◽  
Protein Levels ◽  
Malignant State ◽  
E Boxes

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function.

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