ReviewFrontiers in oncology2014
Complex Interplay between the P-Glycoprotein Multidrug Efflux Pump and the Membrane: Its Role in Modulating Protein Function.
Review in Frontiers in oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 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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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
130 citing papers in PubMed, 272 citations in OpenAlex.
- Synthesis and Assessment of the Enantioselectivity in Antitumor Activity of a Library of Novel Chiral Flavone Derivatives.ChemMedChem · 2026Article
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- Cryo-EM structures of human ABCB7 reveal the molecular basis of mitochondrial matrix heme export.Communications biology · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2025Review
- Mutation and Microsatellite Instability (MSI) Affect the Differential Gene Expression of Folic Acid and 5-Flourouracil Metabolism-Related Genes in Colorectal Carcinoma.Current oncology (Toronto, Ont.) · 2025Article
- Proteome mining of Yersinia Enterocolitica for drug targets and computational inhibitor identification with ADMET, anti-inflammation potential and formulation characteristics.BioData mining · 2025Article
- Elucidating the Complex Structural and Molecular Mechanisms Driving P-Glycoprotein-Mediated Transport of Cardiac Glycosides.International journal of molecular sciences · 2025Article
- P-glycoprotein modulates the fluidity gradient of the plasma membrane of multidrug resistant CHO cells.FEBS letters · 2025Article
- Neisseria meningitidis regulates P-glycoprotein transporter activity in brain endothelial cells via sphingosine 1-phosphate receptor 1.Fluids and barriers of the CNS · 2025Article
- Sensitivity of Tepotinib to Inhibitors or Inducers of CYP3A4 and P-Gp: Drug Interaction Studies and Physiologically-Based Pharmacokinetic Analysis.Clinical and translational science · 2025Article
- Surfactant-Enabled Nanocarriers in Breast Cancer Therapy: Targeted Delivery and Multidrug Resistance Reversal.Pharmaceutics · 2025Review
- P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome.International journal of molecular sciences · 2025Review
- Mapping the Role of P-gp in Multidrug Resistance: Insights from Recent Structural Studies.International journal of molecular sciences · 2025Review
- Cryo-EM of human P-glycoprotein reveals an intermediate occluded conformation during active drug transport.Nature communications · 2025Article
- Reliability of in vitro data for the mechanistic prediction of brain extracellular fluid pharmacokinetics of P-glycoprotein substrates in vivo; are we scaling correctly?Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Functional analysis of Candida albicans Cdr1 through homologous and heterologous expression studies.FEMS yeast research · 2025Review
- Pro-fertility andProtein and peptide letters · 2025Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- Cadmium transport by mammalian ATP-binding cassette transporters.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance in cancer is linked to expression of the P-glycoprotein multidrug transporter (Pgp, ABCB1), which exports many structurally diverse compounds from cells. Substrates first partition into the bilayer and then interact with a large flexible binding pocket within the transporter's transmembrane regions. Pgp has been described as a hydrophobic vacuum cleaner or an outwardly directed drug/lipid flippase. Recent X-ray crystal structures have shed some light on the nature of the drug-binding pocket and suggested routes by which substrates can enter it from the membrane. Detergents have profound effects on Pgp function, and several appear to be substrates. Biochemical and biophysical studies in vitro, some using purified reconstituted protein, have explored the effects of the membrane environment. They have demonstrated that Pgp is involved in a complex relationship with its lipid environment, which modulates the behavior of its substrates, as well as various functions of the protein, including ATP hydrolysis, drug binding, and drug transport. Membrane lipid composition and fluidity, phospholipid headgroup and acyl chain length all influence Pgp function. Recent studies focusing on thermodynamics and kinetics have revealed some important principles governing Pgp-lipid and substrate-lipid interactions, and how these affect drug-binding and transport. In some cells, Pgp is associated with cholesterol-rich microdomains, which may modulate its functions. The relationship between Pgp and cholesterol remains an open question; however, it clearly affects several aspects of its function in addition to substrate-membrane partitioning. The action of Pgp modulators appears to depend on their membrane permeability, and membrane fluidizers and surfactants reverse drug resistance, likely via an indirect mechanism. A detailed understanding of how the membrane affects Pgp substrates and Pgp's catalytic cycle may lead to new strategies to combat clinical drug resistance.
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