ArticleProceedings of the National Academy of Sciences of the United States of America1998
Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
75 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables.European journal of clinical nutrition · 2002Trial
- Integrated machine learning and molecular dynamics framework for predicting and elucidating ABCB1 allocrite interactions.Briefings in bioinformatics · 2026Article
- Impact of Salix mucronata bark and betaine as natural alleviators on semen quality, serum biochemistry, and oxidative capacity in heat-stressed rabbit bucks.Tropical animal health and production · 2025Article
- Antioxidants by nature: an ancient feature at the heart of flavonoids' multifunctionality.The New phytologist · 2025Article
- The plant matrix of Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies.PloS one · 2025Article
- A Molecular Dynamic Simulation, Structural Analysis, and Ex Vivo Insights into the P-glycoprotein Mediated Interactions of Dietary Polyphenols with Cyclin-dependent Kinase Inhibitors: A Potential Strategy to Counteract Drug Efflux.Current medicinal chemistry · 2025Article
- Medicinal plants as a potential resource for the discovery of novel structures towards cancer drug resistance treatment.Heliyon · 2024Review
- ATP modulation of osmotically activated anionic current in the membrane of Phycomyces blakesleeanus sporangiophore.Scientific reports · 2023Article
- Probing the Allosteric Modulation of P-Glycoprotein: A Medicinal Chemistry Approach Toward the Identification of Noncompetitive P-Gp Inhibitors.ACS omega · 2023Article
- Total flavonoids extracted fromFrontiers in pharmacology · 2023Article
- Reckoning apigenin and kaempferol as a potential multi-targeted inhibitor of EGFR/HER2-MEK pathway of metastatic colorectal cancer identified using rigorous computational workflow.Molecular diversity · 2022Article
- The Tetrahydroisoquinoline Scaffold in ABC Transporter Inhibitors that Act as Multidrug Resistance (MDR) Reversers.Current topics in medicinal chemistry · 2022Review
- Review
- Heat Stress in Broiler Chickens and the Effect of Dietary Polyphenols, with Special Reference to Willow (Antioxidants (Basel, Switzerland) · 2021Review
- Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy.Molecules (Basel, Switzerland) · 2021Review
- Naphthylphthalamic acid associates with and inhibits PIN auxin transporters.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The effect of green tea catechins on breast cancer resistance protein activity and intestinal efflux of aflatoxin BToxicological research · 2020Article
- Theoretical insights on helix repacking as the origin of P-glycoprotein promiscuity.Scientific reports · 2020Article
- Molecular interaction and cellular studies on combination photodynamic therapy with rutoside for melanoma A375 cancer cells: an in vitro study.Cancer cell international · 2020Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hexahistidine-tagged C-terminal nucleotide-binding domain (H6-NBD2) from mouse P-glycoprotein was designed, overexpressed, and purified as a highly soluble recombinant protein. Intrinsic fluorescence of its single tryptophan residue allowed monitoring of high-affinity binding of 2'(3')-N-methylanthraniloyl-ATP (MANT-ATP), a fluorescent ATP derivative that induces a marked quenching correlated to fluorescence resonance-energy transfer. H6-NBD2 also bound all flavonoids known to modulate the multidrug resistance phenotype of P-glycoprotein-positive cancer cells, with similar affinities and relative efficiencies. Flavones (like quercetin or apigenin) bound more strongly than flavanones (naringenin), isoflavones (genistein), or glycosylated derivatives (rutin). Kaempferide, a 4'-methoxy 3,5,7-trihydroxy flavone, was even more reactive and induced a complete quenching of H6-NBD2 intrinsic fluorescence. Kaempferide binding was partly prevented by preincubation with ATP, or partly displaced upon ATP addition. Interestingly, kaempferide was also able to partly prevent the binding of the antiprogestin RU 486 to a hydrophobic region similar to that recently found, close to the ATP site, in the N-terminal cytosolic domain. Conversely, RU 486 partly prevented kaempferide binding, the effect being additive to the partial prevention by ATP. Furthermore, MANT-ATP binding, which occurred at the ATP site and extended to the vicinal steroid-interacting hydrophobic region, was completely prevented or displaced by kaempferide. All results indicate that flavonoids constitute a new class of modulators with bifunctional interactions at vicinal ATP-binding site and steroid-interacting region within a cytosolic domain of P-glycoprotein.
Indexed as
Identifiers
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.