publication . Article . 2015

An automated fitting procedure and software for dose-response curves with multiphasic features

Veroli, Giovanni Y. Di; Fornari, Chiara; Goldlust, Ian; Mills, Graham; Koh, Siang Boon; Bramhall, Jo L; Richards, Frances M.; Jodrell, Duncan I.;
Open Access English
  • Published: 01 Oct 2015 Journal: volume 5issn: 2045-2322, eissn: 2045-2322, Copyright policy
  • Publisher: Scientific Reports
Abstract
In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there are instances where the marked presence of more than one point of inflection, or the presence of combined agonist and antagonist effects, prevents straight-forward modelling of the data via a standard Hill equation. Here we propose a modified model and automated fitting procedure to describe dose-response curves with multiphasic features. The resulting general model enables interpreting each phase of the dose-response as an independent dose-dependent process. We developed an algorit...
Subjects
free text keywords: Article
58 references, page 1 of 4

Hollinger M. A.Introduction to Pharmacology (2007).

Timbrell J. A.Principles of Biochemical Toxicology (2008).

Prinz H.Hill coefficients, dose-response curves and allosteric mechanisms. J. Chem. Biol.3, 37–44 (2010).19779939 [OpenAIRE] [PubMed]

Juška A.A minimal model of non-hyperbolic enzyme and receptor kinetics. Biochem. Biophys. Res. Commun.309, 810–814 (2003).13679045 [PubMed]

Lin Y.et al.Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells. Br. J. Cancer 107, 1692–701 (2012).23037716 [OpenAIRE] [PubMed]

Di Veroli G. Y., Davies M. R., Zhang H., Abi-Gerges N. & Boyett M. R. hERG Inhibitors With Similar Potency But Different Binding Kinetics Do Not Pose the Same Proarrhythmic Risk: Implications for Drug Safety Assessment. J. Cardiovasc. Electrophysiol. 25, 197–207 (2014).24118558 [PubMed]

Kalra A. V.et al.Preclinical Activity of Nanoliposomal Irinotecan Is Governed by Tumor Deposition and Intratumor Prodrug Conversion. Cancer Res.74, 7003–7013 (2014).25273092 [PubMed]

Hardwick J., Meyer M. C. & Stout Q. F. Directed Walk Designs for Dose-Response Problems with Competing Failure Modes. Biometrics 59, 229–236 (2003).12926707 [PubMed]

Weinberg R. A.The Biology of Cancer (2007).

Wenner M. M., Wilson T. E., Davis S. L. & Stachenfeld N. S. Pharmacological curve fitting to analyze cutaneous adrenergic responses. J. Appl. Physiol. 111, 1703–9 (2011).21868682 [OpenAIRE] [PubMed]

Prentice R. L.A Generalization of the Probit and Logit Methods for Dose Response Curves. Biometrics 32, 761–768 (1976).1009225 [PubMed]

Keener J. & Sneyd J. Mathematical Physiology: I: Cellular Physiology. (Springer, 2009).

Conolly R. B. & Lutz W. K. Nonmonotonic dose-response relationships: mechanistic basis, kinetic modeling, and implications for risk assessment. Toxicol. Sci. 77, 151–7 (2004).14600281 [PubMed]

Hunt D. L. & Bowman D. A parametric model for detecting hormetic effects in developmental toxicity studies. Risk Anal. 24, 65–72 (2004).15028001 [PubMed]

Giraldo J.On the fitting of binding data when receptor dimerization is suspected. Br. J. Pharmacol.155, 17–23 (2008).18536745 [OpenAIRE] [PubMed]

58 references, page 1 of 4
Abstract
In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there are instances where the marked presence of more than one point of inflection, or the presence of combined agonist and antagonist effects, prevents straight-forward modelling of the data via a standard Hill equation. Here we propose a modified model and automated fitting procedure to describe dose-response curves with multiphasic features. The resulting general model enables interpreting each phase of the dose-response as an independent dose-dependent process. We developed an algorit...
Subjects
free text keywords: Article
58 references, page 1 of 4

Hollinger M. A.Introduction to Pharmacology (2007).

Timbrell J. A.Principles of Biochemical Toxicology (2008).

Prinz H.Hill coefficients, dose-response curves and allosteric mechanisms. J. Chem. Biol.3, 37–44 (2010).19779939 [OpenAIRE] [PubMed]

Juška A.A minimal model of non-hyperbolic enzyme and receptor kinetics. Biochem. Biophys. Res. Commun.309, 810–814 (2003).13679045 [PubMed]

Lin Y.et al.Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells. Br. J. Cancer 107, 1692–701 (2012).23037716 [OpenAIRE] [PubMed]

Di Veroli G. Y., Davies M. R., Zhang H., Abi-Gerges N. & Boyett M. R. hERG Inhibitors With Similar Potency But Different Binding Kinetics Do Not Pose the Same Proarrhythmic Risk: Implications for Drug Safety Assessment. J. Cardiovasc. Electrophysiol. 25, 197–207 (2014).24118558 [PubMed]

Kalra A. V.et al.Preclinical Activity of Nanoliposomal Irinotecan Is Governed by Tumor Deposition and Intratumor Prodrug Conversion. Cancer Res.74, 7003–7013 (2014).25273092 [PubMed]

Hardwick J., Meyer M. C. & Stout Q. F. Directed Walk Designs for Dose-Response Problems with Competing Failure Modes. Biometrics 59, 229–236 (2003).12926707 [PubMed]

Weinberg R. A.The Biology of Cancer (2007).

Wenner M. M., Wilson T. E., Davis S. L. & Stachenfeld N. S. Pharmacological curve fitting to analyze cutaneous adrenergic responses. J. Appl. Physiol. 111, 1703–9 (2011).21868682 [OpenAIRE] [PubMed]

Prentice R. L.A Generalization of the Probit and Logit Methods for Dose Response Curves. Biometrics 32, 761–768 (1976).1009225 [PubMed]

Keener J. & Sneyd J. Mathematical Physiology: I: Cellular Physiology. (Springer, 2009).

Conolly R. B. & Lutz W. K. Nonmonotonic dose-response relationships: mechanistic basis, kinetic modeling, and implications for risk assessment. Toxicol. Sci. 77, 151–7 (2004).14600281 [PubMed]

Hunt D. L. & Bowman D. A parametric model for detecting hormetic effects in developmental toxicity studies. Risk Anal. 24, 65–72 (2004).15028001 [PubMed]

Giraldo J.On the fitting of binding data when receptor dimerization is suspected. Br. J. Pharmacol.155, 17–23 (2008).18536745 [OpenAIRE] [PubMed]

58 references, page 1 of 4
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publication . Article . 2015

An automated fitting procedure and software for dose-response curves with multiphasic features

Veroli, Giovanni Y. Di; Fornari, Chiara; Goldlust, Ian; Mills, Graham; Koh, Siang Boon; Bramhall, Jo L; Richards, Frances M.; Jodrell, Duncan I.;