Aurora kinase inhibitor patents and agents in clinical testing: an update (2011 – 2013)

Abstract

Introduction: Aurora kinase A, B and C, members of serine/threonine kinase family, are key regulators of mitosis. As Aurora kinases are overexpressed in many of the human cancers, small-molecule inhibitors of Aurora kinase have emerged as a possible treatment option for cancer.

Areas covered: In 2009 and 2011, the literature pertaining to Aurora kinase inhibitors and their patents was reviewed. Here, the aim is to update the information for Aurora kinase inhibitors in clinical trials and the patents filed between the years 2011 and 2013. Pubmed, Scopus®, Scifinder®, USPTO, EPO and www.clinicaltrials.gov databases were used for searching the literature and patents for Aurora kinase inhibitors.

Expert opinion: Even though both Aurora sub-type selective as well as pan-selective inhibitors show preclinical and clinical efficacy, so far no Aurora kinase inhibitor has been approved for clinical use. Particularly, dose-limiting toxicity (neutropenia) is a key issue that needs to be addressed. Preliminary evidence suggests that the use of selective Aurora A inhibitors could avoid Aurora B-mediated neutropenia in clinical settings. Also, use of adjunctive agents such as granulocyte stimulating factor to overcome neutropenia associated with Aurora B inhibition could be an answer to overcome the toxicity and bring Aurora inhibitors to market in the future.

Keywords::

• AMG 900 and KW-2449
• AT-9283
• Aurora kinase inhibitor
• AZD1152
• CYC116
• ENMD-2076
• GSK1070916
• MLN8054
• MLN8237
• PF-3814735
• PHA739358
• R763
• SNS-314
• VX-680/MK0457
• VX-689/MK-5108

Acknowledgments

This work was supported by grants (SR/FT/LS-64/2011) of Science & Engineering Research Board, Govt. of India for MS Coumar. S Sarvagalla gratefully acknowledges Department of Biotechnology, Govt. of India, for Junior Research Fellowship (DBT-JRF/2012-13/80). CHA Cheung and S Sarvagalla contributed equally to this work.

This article is an update to Aurora kinase inhibitors review, which appeared in “Expert Opin. Ther. Patents 2009, 19, 1–36, Expert Opin. Investig. Drugs 2009, 18, 1–20 and Expert Opin. Ther. Patents 2011, 21, 857–884”.

Notes

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