ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Multi-species analyses of direct activators of the constitutive androstane receptor.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.International journal of molecular sciences · 2023Article
- Impact of Neonatal Activation of Nuclear Receptor CAR (Nr1i3) on Cyp2 Gene Expression in Adult Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Article
- Review
- Harmonized Cross-Species Assessment of Endocrine and Metabolic Disruptors by Ecotox FACTORIAL Assay.Environmental science & technology · 2020Article
- The Connection of Azole Fungicides with Xeno-Sensing Nuclear Receptors, Drug Metabolism and Hepatotoxicity.Cells · 2020Review
- Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes.Heliyon · 2019Article
- Constitutive androstane receptor 1 is constitutively bound to chromatin and 'primed' for transactivation in hepatocytes.Molecular pharmacology · 2019Article
- In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets.Nucleic acids research · 2018Article
- Impact of CAR Agonist Ligand TCPOBOP on Mouse Liver Chromatin Accessibility.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Human relevance of rodent liver tumour formation by constitutive androstane receptor (CAR) activators.Toxicology research · 2018Review
- Case examples of an evaluation of the human relevance of the pyrethroids/pyrethrins-induced liver tumours in rodents based on the mode of action.Toxicology research · 2018Review
- CINPA1 binds directly to constitutive androstane receptor and inhibits its activity.Biochemical pharmacology · 2018Article
- Sex-Differential Responses of Tumor Promotion-Associated Genes and Dysregulation of Novel Long Noncoding RNAs in Constitutive Androstane Receptor-Activated Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Molecular Basis of Metabolism-Mediated Conversion of PK11195 from an Antagonist to an Agonist of the Constitutive Androstane Receptor.Molecular pharmacology · 2017Article
- Activation of the Constitutive Androstane Receptor by Monophthalates.Chemical research in toxicology · 2016Article
- A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study.Critical reviews in toxicology · 2016Review
- Mechanisms of xenobiotic receptor activation: Direct vs. indirect.Biochimica et biophysica acta · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The constitutive androstane receptor (CAR; NR1I3) is a member of the nuclear receptor superfamily and functions as an important xenochemical sensor and transcriptional modulator in mammalian cells. Upon chemical activation, CAR undergoes nuclear translocation and heterodimerization with the retinoid X receptor subsequent to its DNA target interaction. CAR is unusual among nuclear receptors in that it possesses a high level of constitutive activity in cell-based assays, obscuring the detection of ligand activators. However, a human splice variant of CAR, termed CAR3, exhibits negligible constitutive activity. In addition, CAR3 is activated by ligands with similar specificity as the reference form of the receptor. In this study, we hypothesized that similar CAR3 receptors could be constructed across various mammalian species' forms of CAR that would preserve species-specific ligand responses, thus enabling a more sensitive and differential screening assessment of CAR response among animal models. A battery of CAR3 receptors was produced in mouse, rat, and dog and comparatively evaluated with selected ligands together with human CAR1 and CAR3 in mammalian cell reporter assays. The results demonstrate that the 5-amino acid insertion that typifies human CAR3 also imparts ligand-activated receptor function in other species' CAR while maintaining signature responses in each species to select CAR ligands. These variant constructs permit in vitro evaluation of differential chemical effector responses across species and coupled with in vivo assays, the species-selective contributions of CAR in normal physiology and in disease processes such as hepatocarcinogenesis.
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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.