ArticleScientific reports2015
Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed.
- Article
- Investigating the quantitative toxicological relationship between PFAS alkyl fluorine structure and exposure levels leading to changes in blood-based clinical markers in rats.Journal of toxicology and environmental health. Part A · 2025Article
- The use of tocofersolan as a rescue agent in larval zebrafish exposed to benzo[a]pyrene in early development.Neurotoxicology · 2021Article
- Disease evolution in reaction networks: Implications for a diagnostic problem.PLoS computational biology · 2020Article
- Steady-State Differential Dose Response in Biological Systems.Biophysical journal · 2018Article
- Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G-quadruplex in KChemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Cellular reactions to long-term volatile organic compound (VOC) exposures.Scientific reports · 2016Article
- Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.
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