ArticleBiochemistry2015
Multiple Drug Transport Pathways through Human P-Glycoprotein.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 81 citations in OpenAlex.
- Thioxanthone-Mediated Cytoprotection Against Cisplatin Toxicity: Exploring the Potential Involvement of P-Glycoprotein Through Computational and Experimental Approaches.Journal of xenobiotics · 2026Article
- Simulation and Machine Learning Assessment of P-Glycoprotein Pharmacology in the Blood-Brain Barrier: Inhibition and Substrate Transport.International journal of molecular sciences · 2025Article
- Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- Article
- Membrane-assisted tariquidar access and binding mechanisms of human ATP-binding cassette transporter P-glycoprotein.Frontiers in molecular biosciences · 2024Article
- Article
- Efflux dynamics of the antiseizure drug, levetiracetam, through the P-glycoprotein channel revealed by advanced comparative molecular simulations.Scientific reports · 2022Article
- Effect of natural flavonoids to reverse P-glycoprotein-related multidrug resistance in breast cancer cell cultures.American journal of cancer research · 2022Article
- The role of epithelial-mesenchymal transition-regulating transcription factors in anti-cancer drug resistance.Archives of pharmacal research · 2021Review
- Article
- ABC transporters and the hallmarks of cancer: roles in cancer aggressiveness beyond multidrug resistance.Cancer biology & medicine · 2020Review
- In Silico Investigation of First-Pass Effect on Selected Small Molecule Excipients and Structural Dynamics of P-glycoprotein.Bioinformatics and biology insights · 2020Article
- Article
- Optimizing Targeted Inhibitors of P-Glycoprotein Using Computational and Structure-Guided Approaches.Journal of medicinal chemistry · 2019Article
- Multi-Modulation of Doxorubicin Resistance in Breast Cancer Cells by Poly(l-histidine)-Based Multifunctional Micelles.Pharmaceutics · 2019Article
- Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity.Acta pharmacologica Sinica · 2019Article
- Article
- Novel 3,4-Dihydroisocoumarins Inhibit Human P-gp and BCRP in Multidrug Resistant Tumors and Demonstrate Substrate Inhibition of Yeast Pdr5.Frontiers in pharmacology · 2019Article
- Comparison of mechanistic transport cycle models of ABC exporters.Biochimica et biophysica acta. Biomembranes · 2018Review
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 at 1 institution in 1 country.
Funding
Abstract
P-Glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11-12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methylpyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp is presented.
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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.