ArticleCPT: pharmacometrics & systems pharmacology2013
A mathematical model for the rational design of chimeric ligands in selective drug therapies.
Article in CPT: pharmacometrics & systems pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors.PLoS computational biology · 2024Article
- AI-based identification of therapeutic agents targeting GPCRs: introducing ligand type classifiers and systems biology.Chemical science · 2023Article
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- A kinetic proofreading model for bispecific protein degraders.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control.Journal of optimization theory and applications · 2021Article
- Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology.Clinical pharmacology and therapeutics · 2020Review
- Target-Mediated Drug Disposition Model for Bispecific Antibodies: Properties, Approximation, and Optimal Dosing Strategy.CPT: pharmacometrics & systems pharmacology · 2019Article
- Drug treatment efficiency depends on the initial state of activation in nonlinear pathways.Scientific reports · 2018Article
- General principles of binding between cell surface receptors and multi-specific ligands: A computational study.PLoS computational biology · 2017Article
- The application of mathematical modelling to the design of bispecific monoclonal antibodies.mAbs · 2016Article
- Article
- Designing cell-targeted therapeutic proteins reveals the interplay between domain connectivity and cell binding.Biophysical journal · 2014Article
- A tunable coarse-grained model for ligand-receptor interaction.PLoS computational biology · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.