ArticleBiophysical journal2012
P-glycoprotein-ATPase modulation: the molecular mechanisms.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 50 citations in OpenAlex.
- BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo.Cell communication and signaling : CCS · 2024Article
- Evaluation of Novel Benzo-annelated 1,4-dihydropyridines as MDR Modulators in Cancer Cells.Anti-cancer agents in medicinal chemistry · 2024Article
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- Ligand's Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins.Molecules (Basel, Switzerland) · 2023Article
- Interaction of a Homologous Series of Amphiphiles with P-glycoprotein in a Membrane Environment-Contributions of Polar and Non-Polar Interactions.Pharmaceutics · 2023Article
- P-glycoprotein (ABCB1) - weak dipolar interactions provide the key to understanding allocrite recognition, binding, and transport.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- The potential roles of retinoids in combating drug resistance in cancer: implications of ATP-binding cassette (ABC) transporters.Open biology · 2022Review
- Lazertinib improves the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 overexpression cancer cells iMolecular therapy oncolytics · 2022Article
- Phytol and Heptacosane Are Possible Tools to Overcome Multidrug Resistance in an In Vitro Model of Acute Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites.Frontiers in pharmacology · 2021Review
- Reversal of ABCB1-related multidrug resistance by ERK5-IN-1.Journal of experimental & clinical cancer research : CR · 2020Article
- P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers.Frontiers in oncology · 2020Review
- Comparison of mechanistic transport cycle models of ABC exporters.Biochimica et biophysica acta. Biomembranes · 2018Review
- Unidirectional Transport Mechanism in an ATP Dependent Exporter.ACS central science · 2017Article
- How Phosphorylation and ATPase Activity Regulate Anion Flux though the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).The Journal of biological chemistry · 2016Article
- NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function.British journal of pharmacology · 2016Article
- The DrrAB efflux system of Streptomyces peucetius is a multidrug transporter of broad substrate specificity.The Journal of biological chemistry · 2014Article
- Complex Interplay between the P-Glycoprotein Multidrug Efflux Pump and the Membrane: Its Role in Modulating Protein Function.Frontiers in oncology · 2014Review
- How membrane partitioning modulates receptor activation: parallel versus serial effects of hydrophobic ligands.Biophysical journal · 2013Article
- Article
Corrections and comments
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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
P-glycoprotein-ATPase is an efflux transporter of broad specificity that counteracts passive allocrit influx. Understanding the rate of allocrit transport therefore matters. Generally, the rates of allocrit transport and ATP hydrolysis decrease exponentially with increasing allocrit affinity to the transporter. Here we report unexpectedly strong down-modulation of the P-glycoprotein-ATPase by certain detergents. To elucidate the underlying mechanism, we chose 34 electrically neutral and cationic detergents with different hydrophobic and hydrophilic characteristics. Measurement of the P-glycoprotein-ATPase activity as a function of concentration showed that seven detergents activated the ATPase as expected, whereas 27 closely related detergents reduced it significantly. Assessment of the free energy of detergent partitioning into the lipid membrane and the free energy of detergent binding from the membrane to the transporter revealed that the ratio, q, of the two free energies of binding determined the rate of ATP hydrolysis. Neutral (cationic) detergents with a ratio of q = 2.7 ± 0.2 (q > 3) followed the aforementioned exponential dependence. Small deviations from the optimal ratio strongly reduced the rates of ATP hydrolysis and flopping, respectively, whereas larger deviations led to an absence of interaction with the transporter. P-glycoprotein-ATPase inhibition due to membrane disordering by detergents could be fully excluded using (2)H-NMR-spectroscopy. Similar principles apply to modulating drugs.
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What OpenQuestion holds
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.