DoldánMartelli2013 - A Mathematical Model for the Rational Design of Chimeric Ligands in Selective Drug Therapies
Model Identifier
MODEL1907310001
Short description
This model attempts to provide a mathematical framework for describing the dynamics of receptor-drug complex formation of chimeric drugs.
Format
SBML
(L2V4)
Related Publication
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A mathematical model for the rational design of chimeric ligands in selective drug therapies.
- Doldán-Martelli V, Guantes R, Míguez DG
- CPT: pharmacometrics & systems pharmacology , 1/ 2013 , Volume 2 , pages: e26 , PubMed ID: 23887616
- Departamento de Física de la Materia Condensada and Instituto Nicolás Cabrera, and IFIMAC Universidad Autónoma de Madrid, Facultad de Ciencias, Madrid, Spain.
- Chimeric drugs with selective potential toward specific cell types constitute one of the most promising forefronts of modern Pharmacology. We present a mathematical model to test and optimize these synthetic constructs, as an alternative to conventional empirical design. We take as a case study a chimeric construct composed of epidermal growth factor (EGF) linked to different mutants of interferon (IFN). Our model quantitatively reproduces all the experimental results, illustrating how chimeras using mutants of IFN with reduced affinity exhibit enhanced selectivity against cell overexpressing EGF receptor. We also investigate how chimeric selectivity can be improved based on the balance between affinity rates, receptor abundance, activity of ligand subunits, and linker length between subunits. The simplicity and generality of the model facilitate a straightforward application to other chimeric constructs, providing a quantitative systematic design and optimization of these selective drugs against certain cell-based diseases, such as Alzheimer's and cancer.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e26; doi:10.1038/psp.2013.2; advance online publication 13 February 2013.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Metadata information
Curation status
Non-curated
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| DoldánMartelli2013.xml | SBML L2V4 Representation of DoldánMartelli2013 - A Mathematical Model for the Rational Design of Chimeric Ligands in Selective Drug Therapies | 50.30 KB | Preview | Download |
Additional files |
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| DoldánMartelli2013.cps | COPASI file of DoldánMartelli2013 - A Mathematical Model for the Rational Design of Chimeric Ligands in Selective Drug Therapies | 98.03 KB | Preview | Download |
- Model originally submitted by : Johannes Meyer
- Submitted: Jul 31, 2019 10:22:44 AM
- Last Modified: Jul 31, 2019 10:22:44 AM
Revisions
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Version: 2
- Submitted on: Jul 31, 2019 10:22:44 AM
- Submitted by: Johannes Meyer
- With comment: Edited model metadata online.