ArticlePLoS computational biology2018
Determinants of drug-target interactions at the single cell level.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed.
- Spatial pharmacology of anti-cancer immunomodulators: a comprehensive review.Frontiers in pharmacology · 2026Review
- Advanced imaging techniques for tracking drug dynamics at the subcellular level.Advanced drug delivery reviews · 2023Review
- Local generation and efficient evaluation of numerous drug combinations in a single sample.eLife · 2023Article
- Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases.Journal of personalized medicine · 2022Review
- Wide-range viscoelastic compression forces in microfluidics to probe cell-dependent nuclear structural and mechanobiological responses.Journal of the Royal Society, Interface · 2022Article
- A Subject-Tailored Variability-Based Platform for Overcoming the Plateau Effect in Sports Training: A Narrative Review.International journal of environmental research and public health · 2022Review
- A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System.Polymers · 2021Article
- Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm.Frontiers in cardiovascular medicine · 2021Review
- Targeting SARS-CoV-2 receptors as a means for reducing infectivity and improving antiviral and immune response: an algorithm-based method for overcoming resistance to antiviral agents.Emerging microbes & infections · 2020Review
- Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects.Molecular therapy. Methods & clinical development · 2020Review
- The potential roles of Von Willebrand factor and neutrophil extracellular traps in the natural history of hypertrophic and hypertensive cardiomyopathy.Thrombosis research · 2020Review
- Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways.International journal of nanomedicine · 2020Article
- Second-Generation Digital Health Platforms: Placing the Patient at the Center and Focusing on Clinical Outcomes.Frontiers in digital health · 2020Article
- Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physiochemical determinants of drug-target interactions in the microenvironment of the cell are complex and generally not defined by simple diffusion and intrinsic chemical reactivity. Non-specific interactions of drugs and macromolecules in cells are rarely considered formally in assessing pharmacodynamics. Here, we demonstrate that non-specific interactions lead to very slow incorporation kinetics of DNA binding drugs. We observe a rate of drug incorporation in cell nuclei three orders of magnitude slower than in vitro due to anomalous drug diffusion within cells. This slow diffusion, however, has an advantageous consequence: it leads to virtually irreversible binding of the drug to specific DNA targets in cells. We show that non-specific interactions drive slow drug diffusion manifesting as slow reaction front propagation. We study the effect of non-specific interactions in different cellular compartments by permeabilization of plasma and nuclear membranes in order to pinpoint differential compartment effects on variability in intracellular drug kinetics. These results provide the basis for a comprehensive model of the determinants of intracellular diffusion of small-molecule drugs, their target-seeking trajectories, and the consequences of these processes on the apparent kinetics of drug-target interactions.
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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.