Rat Constitutive Androstane Receptor (rCAR; nr1i3)
Because this assay system expresses the [GAL4-DBD + rCAR LBD] hybrid receptor, the activity of modulators that act through indirect mechanisms (such as those that alter the phosphorylation status of the native N-terminal amino acid sequence of the CARs) may be dampened or go undetected.
True to its name, rat CAR is constitutionally active, but this activity may be further modulated through ligand interactions that deliver inverse-agonism responses.
For more information on CAR, visit the Nuclear Receptor Resource.
The primary application of INDIGO’s cell-based nuclear receptor assays are to quantitatively assess the bioactivity of a test compound as an agonist (activator) or antagonist (inhibition of an agonist response) of a given receptor. Service assays include a positive control reference compound and ‘vehicle’ control for every experiment. A formal study report and all data files are provided to the client upon completion of the study. To receive a quote for your proposed study, complete & submit the online “Request a Quote” form or contact an INDIGO Customer Service Representative to discuss your desired study parameters. To initiate a Service Study, download and complete all fields of the Excel worksheet “Service Work Order" then submit the electronic file to INDIGO Customer Service.
Sedaxane—Use of Nuclear Receptor Transactivation Assays, Toxicogenomics, and Toxicokinetics as Part of a Mode of Action Framework for Rodent Liver Tumors
ABSTRACT Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA is
View Full Size Research conducted by: Koji Toyokawa (1), Ewa Maddox (1), Jack Vanden Huevel (1,2), & Bruce Sherf (1) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences Building, Penn State University, University Park, PA 16802, USA Date of Publication: 2017
ABSTRACT Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10 K chemical collection. In the present study, we
Mouse Liver Tumor Mode of Action: Use of Toxicogenomics in Weight of Evidence for Human Relevance Assessment
ABSTRACT The Use of Toxicogenomics in Chemical Safety Testing Current safety testing is geared to produce and accept descriptive data from high-dose animal studies Interpretation of this information has effectively protected our health and safety for decates; however, hindered by lack of understanding mechanistic information Concern over chemical safety for humans and the environment has
ABSTRACT Exposure to certain munitions compounds is know to alter physiological functions in test organisms, however little is known about their molecular and cellular effects. Several nuclear receptors are regulated by xenobiotic compounds. These nuclear receptors belong to a class of ligand-activated transcription factors that, when heterodimerized with RXRa and bound to their respective DNA
In vitro toxicology platform provides predictive model of liver toxicity. Aims to reduce the high rates of drug-induced liver damage State College, PA (May 4, 2016) INDIGO Biosciences, the recognized industry leader in nuclear receptor research, has completed development of an in vitro toxicology platform, meeting the demand for predictive liver toxicity models. INDIGO’s in
ABSTRACT The RAR-related orphan receptor gamma t (RORγt) is a nuclear receptor required for generating IL-17–producing CD4+ Th17 T cells, which are essential in host defense and may play key pathogenic roles in autoimmune diseases. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol and lipid metabolism. Here, we describe the identification of several naturally occurring
ABSTRACT The bacteriostat triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) (TCS) decreases rat serum thyroxine via putative nuclear receptor (NR) interaction(s) and subsequent transcriptional up-regulation of hepatic catabolism and clearance. However, due to the evolutionary divergence of the constitutive androstane and pregnane-X receptors (CAR, PXR), TCS-mediated downstream effects may be species-dependent. To test the hypothesis that TCS activates xenobiotic NRs