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Open Access 01-12-2012 | REVIEW

Aurora kinase inhibitors: Progress towards the clinic

Authors: Madhu Kollareddy, Daniella Zheleva, Petr Dzubak, Pathik Subhashchandra Brahmkshatriya, Martin Lepsik, Marian Hajduch

Published in: Investigational New Drugs | Issue 6/2012

Summary

The Aurora kinases (serine/threonine kinases) were discovered in 1995 during studies of mutant alleles associated with abnormal spindle pole formation in Drosophila melanogaster. They soon became the focus of much attention because of their importance in human biology and association with cancer. Aurora kinases are essential for cell division and are primarily active during mitosis. Following their identification as potential targets for cancer chemotherapy, many Aurora kinase inhibitors have been discovered, and are currently under development. The binding modes of Aurora kinase inhibitors to Aurora kinases share specific hydrogen bonds between the inhibitor core and the back bone of the kinase hinge region, while others parts of the molecules may point to different parts of the active site via noncovalent interactions. Currently there are about 30 Aurora kinase inhibitors in different stages of pre-clinical and clinical development. This review summarizes the characteristics and status of Aurora kinase inhibitors in preclinical, Phase I, and Phase II clinical studies, with particular emphasis on the mechanisms of action and resistance to these promising anticancer agents. We also discuss the validity of Aurora kinases as oncology targets, on/off-target toxicities, and other important aspects of overall clinical performance and future of Aurora kinase inhibitors.

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Title: Aurora kinase inhibitors: Progress towards the clinic
Authors: Madhu Kollareddy
Daniella Zheleva
Petr Dzubak
Pathik Subhashchandra Brahmkshatriya
Martin Lepsik
Marian Hajduch
Publication date: 01-12-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 6/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-012-9798-6

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Other articles of this Issue 6/2012

Phase I and pharmacokinetic study of dacomitinib (PF-00299804), an oral irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases, in Japanese patients with advanced solid tumors

Renal dysfunction in a renal transplant patient treated concurrently with cyclosporine and imatinib

A phase II trial of Erlotinib in combination with gemcitabine and cisplatin in advanced pancreatic cancer

Severe meningo-radiculo-nevritis associated with ipilimumab

(+)-Episesamin exerts anti-neoplastic effects in human hepatocellular carcinoma cell lines via suppression of nuclear factor-kappa B and inhibition of MMP-9

Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer