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A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint

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A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint. / Mistry, Hitesh B.; MacCallum, David E.; Jackson, Robert C.; Chaplain, Mark A. J.; Davidson, Fordyce A.

In: Frontiers in Bioscience, Vol. 15, No. 1, 2010, p. 249-258.

Research output: Contribution to journalArticle

Harvard

Mistry, HB, MacCallum, DE, Jackson, RC, Chaplain, MAJ & Davidson, FA 2010, 'A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint' Frontiers in Bioscience, vol 15, no. 1, pp. 249-258., 10.2741/3619

APA

Mistry, H. B., MacCallum, D. E., Jackson, R. C., Chaplain, M. A. J., & Davidson, F. A. (2010). A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint. Frontiers in Bioscience, 15(1), 249-258. 10.2741/3619

Vancouver

Mistry HB, MacCallum DE, Jackson RC, Chaplain MAJ, Davidson FA. A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint. Frontiers in Bioscience. 2010;15(1):249-258. Available from: 10.2741/3619

Author

Mistry, Hitesh B.; MacCallum, David E.; Jackson, Robert C.; Chaplain, Mark A. J.; Davidson, Fordyce A. / A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint.

In: Frontiers in Bioscience, Vol. 15, No. 1, 2010, p. 249-258.

Research output: Contribution to journalArticle

Bibtex - Download

@article{f549cd40c96445bd9ca5c4bc5144c4d3,
title = "A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint",
keywords = "Spindle assembly checkpoint, Aurora kinase",
author = "Mistry, {Hitesh B.} and MacCallum, {David E.} and Jackson, {Robert C.} and Chaplain, {Mark A. J.} and Davidson, {Fordyce A.}",
year = "2010",
doi = "10.2741/3619",
volume = "15",
number = "1",
pages = "249--258",
journal = "Frontiers in Bioscience",
issn = "1093-9946",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint

A1 - Mistry,Hitesh B.

A1 - MacCallum,David E.

A1 - Jackson,Robert C.

A1 - Chaplain,Mark A. J.

A1 - Davidson,Fordyce A.

AU - Mistry,Hitesh B.

AU - MacCallum,David E.

AU - Jackson,Robert C.

AU - Chaplain,Mark A. J.

AU - Davidson,Fordyce A.

PY - 2010

Y1 - 2010

N2 - Arguably the most dramatic phase in the cell cycle is mitosis, during which replicated chromosomes are sorted into two distinct sets. Aurora kinases are central to the accurate segregation of chromosomes during mitosis. Consequently, they have been selected as possible targets for cancer therapy. Anti-cancer drugs that target Aurora kinases are normally designed to inhibit their function. The complexity of the roles of Aurora kinases and their interaction with respective inhibitors means that it is often very difficult to obtain meaningful links between inhibitor concentration and efficacy using standard methods. To overcome these difficulties, we propose a novel mathematical modelling approach. We present a pharmacodynamic model that is able to encapsulate the key roles of two kinases, Aurora A and B, in the spindle assembly checkpoint. Moreover, the model is capable of qualitatively differentiating between the effects of inhibiting Aurora A, Aurora B and A plus B, respectively, by predicting cell behaviour. Consequently, predictions regarding the qualitative relationship between inhibitors, measurable biomarkers and cell damage can be obtained using this powerful modelling approach.

AB - Arguably the most dramatic phase in the cell cycle is mitosis, during which replicated chromosomes are sorted into two distinct sets. Aurora kinases are central to the accurate segregation of chromosomes during mitosis. Consequently, they have been selected as possible targets for cancer therapy. Anti-cancer drugs that target Aurora kinases are normally designed to inhibit their function. The complexity of the roles of Aurora kinases and their interaction with respective inhibitors means that it is often very difficult to obtain meaningful links between inhibitor concentration and efficacy using standard methods. To overcome these difficulties, we propose a novel mathematical modelling approach. We present a pharmacodynamic model that is able to encapsulate the key roles of two kinases, Aurora A and B, in the spindle assembly checkpoint. Moreover, the model is capable of qualitatively differentiating between the effects of inhibiting Aurora A, Aurora B and A plus B, respectively, by predicting cell behaviour. Consequently, predictions regarding the qualitative relationship between inhibitors, measurable biomarkers and cell damage can be obtained using this powerful modelling approach.

KW - Spindle assembly checkpoint

KW - Aurora kinase

U2 - 10.2741/3619

DO - 10.2741/3619

M1 - Article

JO - Frontiers in Bioscience

JF - Frontiers in Bioscience

SN - 1093-9946

IS - 1

VL - 15

SP - 249

EP - 258

ER -

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