Evidence map›Paper›PMID 29200287›Full record

ArticleBiochemistry2018

Drug-Drug Interactions between Atorvastatin and Dronedarone Mediated by Monomeric CYP3A4.

Ilia G Denisov, Javier L Baylon, Yelena V Grinkova, Emad Tajkhorshid, Stephen G Sligar

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
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  4. [European journal of nuclear medicine and molecular imaging · 2023
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021
    Review
  10. Article
  11. Article
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  13. Article
  14. Article
  15. Ligand Access Channels in Cytochrome P450 Enzymes: A Review.International journal of molecular sciences · 2018
    Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Ilia G DenisovDepartment of Biochemistry, ‡Center for Biophysics and Quantitative Biology, and §Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Javier L BaylonDepartment of Biochemistry, ‡Center for Biophysics and Quantitative Biology, and §Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Yelena V GrinkovaDepartment of Biochemistry, ‡Center for Biophysics and Quantitative Biology, and §Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Emad TajkhorshidDepartment of Biochemistry, ‡Center for Biophysics and Quantitative Biology, and §Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.ORCID 0000-0001-8434-1010
Stephen G SligarDepartment of Biochemistry, ‡Center for Biophysics and Quantitative Biology, and §Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.ORCID 0000-0002-5548-2866
University of Illinois Urbana-Champaign · US

Funding

WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Nanoscale Approaches to Understanding Membrane Protein FunctionR35GM118145 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI STEPHEN G. SLIGAR · 2016 to 2026
$7.5M
Understanding the role of phospholipids in integrin signalingR01GM101048 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SLIGAR, STEPHEN G. · 2012 to 2015
$1.1M
NIGMS NIH HHS P41 GM104601NIGMS NIH HHS R01 GM101048NIGMS NIH HHS R35 GM118145
6 · The paper itself

Abstract

Heterotropic interactions between atorvastatin (ARVS) and dronedarone (DND) have been deciphered using global analysis of the results of binding and turnover experiments for pure drugs and their mixtures. The in vivo presence of atorvastatin lactone (ARVL) was explicitly taken into account by using pure ARVL in analogous experiments. Both ARVL and ARVS inhibit DND binding and metabolism, while a significantly higher affinity of CYP3A4 for ARVL makes the latter the main modulator of activity (effector) in this system. Molecular dynamics simulations reveal significantly different modes of interactions of DND and ARVL with the substrate binding pocket and with a peripheral allosteric site. Interactions of both substrates with residues F213 and F219 at the allosteric site play a critical role in the communication of conformational changes induced by effector binding to productive binding of the substrate at the catalytic site.

Indexed as

Allosteric RegulationAllosteric SiteAmiodaroneAnimalsAtorvastatinBinding SitesCytochrome P-450 CYP3ADose-Response Relationship, DrugDronedaroneDrug InteractionsHumansKineticsModels, MolecularMolecular Dynamics SimulationNADPH-Ferrihemoprotein ReductaseProtein BindingAmiodaroneAtorvastatinCYP3A4 protein, humanCytochrome P-450 CYP3ADronedaroneNADPH-Ferrihemoprotein Reductase

Identifiers

PMID29200287
PMCPMC5800941
OpenAlexW2773241338

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.