Open Access Highly Accessed Research article

Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity

Michelle L Wynn1, Alejandra C Ventura25, Jacques A Sepulchre3, Héctor J García4 and Sofia D Merajver15*

Author Affiliations

1 Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA

2 Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, Argentina

3 Institut Non Linéaire de Nice, Université de Nice Sophia-Antipolis, UMR CNRS 6618, Valbonne, France

4 Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA

5 Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA

For all author emails, please log on.

BMC Systems Biology 2011, 5:156  doi:10.1186/1752-0509-5-156

Published: 4 October 2011

Additional files

Additional file 1:

Mapping dimensionless parameters to dimensional parameters. This file describes how randomly sampled dimensionless parameter values were mapped to dimensional parameter values prior to numeric simulation.

Format: PDF Size: 495KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 2:

Parameter space sampling to estimate the probability of off-target effects. This file describes how the parameter space of a network was sampled to provide an estimate of the probability of off-target effects due to retroactivity alone.

Format: PDF Size: 472KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 3:

Additional analysis of the n = 3 and extended n = 3 networks. This file provides additional results from the numeric perturbation analyses of the n = 3 and extended n = 3 networks.

Format: PDF Size: 949KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 4:

Xenopus MAPK Model Parameters [18,27,28]. This file explains how the Xenopus model parameters listed in Table 2 were derived.

Format: PDF Size: 263KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data