ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Identification of Modulators That Activate the Constitutive Androstane Receptor From the Tox21 10K Compound Library.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Use of Tox21 screening data to profile PFAS bioactivities on nuclear receptors, cellular stress pathways, and cytochrome p450 enzymes.Journal of hazardous materials · 2024Article
- High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions.Annual review of pharmacology and toxicology · 2024Review
- Identification of human pregnane X receptor antagonists utilizing a high-throughput screening platform.Frontiers in pharmacology · 2024Article
- Quantitative Bioactivity Signatures of Dietary Supplements and Natural Products.ACS pharmacology & translational science · 2023Article
- Screening Method for the Identification of Compounds That Activate Pregnane X Receptor.Current protocols · 2022Article
- High-Throughput Chemical Screening and Structure-Based Models to Predict hERG Inhibition.Biology · 2022Article
- Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways.Frontiers in pharmacology · 2022Review
- A Quantitative High-Throughput Screening Data Analysis Pipeline for Activity Profiling.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Identifying CAR Modulators Utilizing a Reporter Gene Assay.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR).Journal of toxicologic pathology · 2021Article
- Characterization of human pregnane X receptor activators identified from a screening of the Tox21 compound library.Biochemical pharmacology · 2021Article
- Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor.Cells · 2020Review
- Application of In Vitro Metabolism Activation in High-Throughput Screening.International journal of molecular sciences · 2020Review
- Review
- 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
- High-content analysis of constitutive androstane receptor (CAR) translocation identifies mosapride citrate as a CAR agonist that represses gluconeogenesis.Biochemical pharmacology · 2019Article
- Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies.European journal of medicinal chemistry · 2019Article
- Prediction Model with High-Performance Constitutive Androstane Receptor (CAR) Using DeepSnap-Deep Learning Approach from the Tox21 10K Compound Library.International journal of molecular sciences · 2019Article
- DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor.ACS medicinal chemistry letters · 2019Article
- Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
8 authors.
Funding
Abstract
The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor involved in all phases of drug metabolism and disposition. However, recently it's been implicated in energy metabolism, tumor progression, and cancer therapy as well. It is, therefore, important to identify compounds that induce human CAR (hCAR) activation to predict drug-drug interactions and potential therapeutic usage. In this study, we screen the Tox21 10,000 compound collection to characterize hCAR activators. A potential novel structural cluster of compounds was identified, which included nitazoxanide and tenonitrozole, whereas known structural clusters, such as flavones and prazoles, were also detected. Four compounds, neticonazole, diphenamid, phenothrin, and rimcazole, have been identified as novel hCAR activators, one of which, rimcazole, shows potential selectivity toward hCAR over its sister receptor, the pregnane X receptor (PXR). All 4 compounds translocated hCAR from the cytoplasm into the nucleus demonstrating the first step to CAR activation. Profiling these compounds as hCAR activators would enable an estimation of drug-drug interactions, as well as identify prospective therapeutically beneficial drugs.
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