ArticleToxicology in vitro : an international journal published in association with BIBRA2016
Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Integrated Approach of Machine Learning and High-Throughput Screening to Identify Chemical Probe Candidates Targeting Aldehyde Dehydrogenases.ACS pharmacology & translational science · 2025Article
- Development and validation of CYP26A1 inhibition assay for high-throughput screening.Biotechnology journal · 2024Article
- Article
- Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways.Frontiers in pharmacology · 2022Review
- Computational model for fetal skeletal defects potentially linked to disruption of retinoic acid signaling.Frontiers in pharmacology · 2022Article
- Molecular Image-Based Prediction Models of Nuclear Receptor Agonists and Antagonists Using the DeepSnap-Deep Learning Approach with the Tox21 10K Library.Molecules (Basel, Switzerland) · 2020Article
- Identification and Profiling of Environmental Chemicals That Inhibit the TGFβ/SMAD Signaling Pathway.Chemical research in toxicology · 2019Article
- Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling.
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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.