Evidence map›Paper›PMID 29430850›Full record

ArticleChemMedChem2018

Probing Ligand Structure-Activity Relationships in Pregnane X Receptor (PXR): Efavirenz and 8-Hydroxyefavirenz Exhibit Divergence in Activation.

Bhargavi Narayanan, Julie M Lade, Carley J S Heck, Kevin D Dietz, Herschel Wade, Namandjé N Bumpus

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Bhargavi NarayananDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Hunterian 709, Baltimore, MD, USA.
Julie M LadeDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Biophysics 307, Baltimore, MD, USA.
Carley J S HeckDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Biophysics 307, Baltimore, MD, USA.
Kevin D DietzDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Hunterian 709, Baltimore, MD, USA.
Herschel WadeDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Hunterian 709, Baltimore, MD, USA.ORCID 0000-0003-1095-7888
Namandjé N BumpusDepartment of Medicine, Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Biophysics 307, Baltimore, MD, USA.ORCID 0000-0002-6096-3824
Johns Hopkins University · US

Funding

Cellular Signaling in Drug Induced ToxicityR01GM103853 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ORSBURN, BENJAMIN CARL · 2013 to 2022
$3.6M
NIGMS NIH HHS R01 GM103853
6 · The paper itself

Abstract

Efavirenz (EFV), an antiretroviral that interacts clinically with co-administered drugs via activation of the pregnane X receptor (PXR), is extensively metabolized by the cytochromes P450. We tested whether its primary metabolite, 8-hydroxyEFV (8-OHEFV) can activate PXR and potentially contribute to PXR-mediated drug-drug interactions attributed to EFV. Luciferase reporter assays revealed that despite only differing from EFV by an oxygen atom, 8-OHEFV does not activate PXR. Corroborating this, treatment with EFV for 72 h elevated the mRNA abundance of the PXR target gene, Cyp3a11, by approximately 28-fold in primary hepatocytes isolated from PXR-humanized mice, whereas treatment with 8-OHEFV did not result in a change in Cyp3A11 mRNA levels. FRET-based competitive binding assays and isothermal calorimetry demonstrated that even with the lack of ability to activate PXR, 8-OHEFV displays an affinity for PXR (IC

Indexed as

AlkynesAnimalsBenzoxazinesBinding SitesCyclopropanesHepatocytesHumansLigandsMiceMolecular Docking SimulationMolecular StructurePregnane X ReceptorProtein BindingStructure-Activity Relationship8-hydroxyefavirenzAlkynesBenzoxazinesCyclopropanesefavirenzLigandsPregnane X Receptorcytochrome P450drug metabolismligand bindingmolecular dockingnuclear receptors

Identifiers

PMID29430850
PMCPMC6081956
OpenAlexW2789578135

What OpenQuestion holds

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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.