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Review
. 2015 Dec 21:5:278.
doi: 10.3389/fonc.2015.00278. eCollection 2015.

Aurora Kinase Inhibitors: Current Status and Outlook

Vassilios Bavetsias  1 , Spiros Linardopoulos  2
Affiliations
Review

Aurora Kinase Inhibitors: Current Status and Outlook

Vassilios Bavetsias et al. Front Oncol. .

Abstract

The Aurora kinase family comprises of cell cycle-regulated serine/threonine kinases important for mitosis. Their activity and protein expression are cell cycle regulated, peaking during mitosis to orchestrate important mitotic processes including centrosome maturation, chromosome alignment, chromosome segregation, and cytokinesis. In humans, the Aurora kinase family consists of three members; Aurora-A, Aurora-B, and Aurora-C, which each share a conserved C-terminal catalytic domain but differ in their sub-cellular localization, substrate specificity, and function during mitosis. In addition, Aurora-A and Aurora-B have been found to be overexpressed in a wide variety of human tumors. These observations led to a number of programs among academic and pharmaceutical organizations to discovering small molecule Aurora kinase inhibitors as anti-cancer drugs. This review will summarize the known Aurora kinase inhibitors currently in the clinic, and discuss the current and future directions.

Keywords: aurora kinase; hematologic diseases; kinase inhibitors; neuroblastoma; small molecules.

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Figures

Figure 1
Figure 1
Aurora-A and Aurora-B localization. Aurora-A (yellow) localizes at the centrosome during interphase and at the mitotic poles and the adjacent spindle microtubules during mitosis. Aurora-B (green) localizes at the chromosomes in prophase, the centromere in prometaphase and metaphase, and the central mitotic spindle in anaphase.
Figure 2
Figure 2
Aurora-A and Aurora-B inhibition induces mitotic aberrations. (A) Aurora-A inhibition induces temporarily a mitotic arrest, cells exit from mitosis with multipolar and monopolar spindle formation leading to apoptosis. (B) Aurora-B inhibition induces endoredublication, chromosome misalignments, and polyploidy.
Figure 3
Figure 3
Schematic representation of Aurora inhibitor-targeted pathways. (A) Selective inhibition of Aurora-A or Aurora-B or dual specificity Aurora/FLT3 compounds induces cytokinesis failure and inhibition of leukemic proliferation. (B) Conformational changes of Aurora-A by a compound induce Aurora-A-FBXW7-MYCN complex disassembly and proteolytic degradation of MYCN. (C) Aurora-A is involved in DNA repair pathways and Aurora-A inhibitors confer increased cellular sensitivity to cell death.
See this image and copyright information in PMC

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