Evidence map›Paper›PMID 38863121›Full record

ArticleBiotechnology journal2024

Development and validation of CYP26A1 inhibition assay for high-throughput screening.

Srilatha Sakamuru, Dongping Ma, Jocylin D Pierro, Nancy C Baker, Nicole Kleinstreuer, James J Cali, Thomas B Knudsen, Menghang Xia

Abstract read
In one paragraph

Article in Biotechnology journal, 2024. 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. Review
  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

8 authors.

Srilatha SakamuruDivision of Pre-clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.
Dongping MaPromega Corporation, Madison, Wisconsin, USA.
Jocylin D PierroCenter for Computational Toxicology and Exposure, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Nancy C BakerLeidos, Research Triangle Park, North Carolina, USA.
Nicole KleinstreuerNational Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
James J CaliPromega Corporation, Madison, Wisconsin, USA.
Thomas B KnudsenCenter for Computational Toxicology and Exposure, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Menghang XiaDivision of Pre-clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0001-7285-8469

Funding

Toxicology in the 21st Century Program (Tox21) - Systems ToxicologyZIATR000038 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI XIA, MENGHANG · 2015 to 2025
$5.7M
Intramural NIH HHS ZIA TR000038
6 · The paper itself

Abstract

All-trans retinoic acid (atRA) is an endogenous ligand of the retinoic acid receptors, which heterodimerize with retinoid X receptors. AtRA is generated in tissues from vitamin A (retinol) metabolism to form a paracrine signal and is locally degraded by cytochrome P450 family 26 (CYP26) enzymes. The CYP26 family consists of three subtypes: A1, B1, and C1, which are differentially expressed during development. This study aims to develop and validate a high throughput screening assay to identify CYP26A1 inhibitors in a cell-free system using a luminescent P450-Glo assay technology. The assay performed well with a signal to background ratio of 25.7, a coefficient of variation of 8.9%, and a Z-factor of 0.7. To validate the assay, we tested a subset of 39 compounds that included known CYP26 inhibitors and retinoids, as well as positive and negative control compounds selected from the literature and/or the ToxCast/Tox21 portfolio. Known CYP26A1 inhibitors were confirmed, and predicted CYP26A1 inhibitors, such as chlorothalonil, prochloraz, and SSR126768, were identified, demonstrating the reliability and robustness of the assay. Given the general importance of atRA as a morphogenetic signal and the localized expression of Cyp26a1 in embryonic tissues, a validated CYP26A1 assay has important implications for evaluating the potential developmental toxicity of chemicals.

Indexed as

High-Throughput Screening AssaysRetinoic Acid 4-HydroxylaseCytochrome P-450 Enzyme InhibitorsHumansReproducibility of ResultsTretinoinCytochrome P-450 Enzyme InhibitorsRetinoic Acid 4-HydroxylaseTretinoinall‐trans retinoic acid (atRA)CYP26cytochrome P450 (CYP)retinoic acid receptor (RAR)

Identifiers

PMID38863121
PMCPMC11338008

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Registered trials

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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.