Evidence map›Paper›PMID 40507787›Full record

ArticleInternational journal of molecular sciences2025

Profiling the Tox21 Compound Library for Their Inhibitory Effects on Cytochrome P450 Enzymes.

Srilatha Sakamuru, Jameson Travers, Carleen Klumpp-Thomas, Ruili Huang, Kristine L Witt, Stephen S Ferguson, Steven O Simmons, David M Reif, Anton Simeonov, Menghang Xia

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

10 authors.

Srilatha SakamuruDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.ORCID 0000-0002-9693-1832
Jameson TraversDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Carleen Klumpp-ThomasDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Ruili HuangDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Kristine L WittDivision of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC 27709, USA.ORCID 0000-0002-3827-6884
Stephen S FergusonDivision of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC 27709, USA.ORCID 0000-0003-3172-8347
Steven O SimmonsCenter for Computational Toxicology & Exposure, U.S. Environmental Protection Agency, Durham, NC 27711, USA.ORCID 0000-0001-9079-1069
David M ReifDivision of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC 27709, USA.ORCID 0000-0001-7815-6767
Anton SimeonovDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Menghang XiaDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.ORCID 0000-0001-7285-8469

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins crucial for drug and xenobiotic metabolism. While more than 50 CYPs have been identified in humans, the isoforms from CYP1, 2, and 3 families contribute to the metabolism of about 80% of clinically approved drugs. To evaluate the effects of environmental chemicals on the activities of these important CYP enzyme families, we screened the Tox21 10K compound library to identify chemicals that inhibit CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes. The data obtained from these five screenings were analyzed to reveal the structural classes responsible for inhibiting multiple and/or selective CYPs. Some known structural compound classes exhibiting pan-CYP inhibition, such as azole fungicides, along with established clinical inhibitors of CYPs, including erythromycin and verapamil inhibiting CYP3A4 and paroxetine and terbinafine inhibiting CYP2D6, were all confirmed in the current study. In addition, some selective CYP inhibitors, previously unknown but with potent activity (IC

Indexed as

Cytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemSmall Molecule LibrariesHumansCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemSmall Molecule LibrariesCYP1A2CYP2C19CYP2C9CYP2D6CYP3A4CYP inhibitorscytochrome P450 (CYP)quantitative high-throughput screening (qHTS)

Identifiers

PMID40507787
PMCPMC12155096

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.