Farnesoid X Receptor (FXR; NR1H4)
These FXR Reporter Assay Systems utilize non-human mammalian cells engineered to express human NR1H4 protein, commonly referred to as FXR.
The farnesoid X receptor (FXR), also known as NR1H4 is a nuclear hormone receptor with activity similar to that seen in other steroid receptors such as estrogen or progesterone receptor, but more similar in form to PPAR, LXR and RXR. Encoded by the NR1H4 gene, FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR.
Like other steroid receptors, when activated, FXR translocates to the cell nucleus, forms a heterodimer with RXR and binds to hormone response elements on DNA (FXEs) to elicit expression or transrepression of gene products. One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP) which then functions to inhibit transcription of the CYP7A1 gene. In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels is already high.
For more information on FXR, visit the Nuclear Receptor Resource.
Kits are offered in different assay formats to accommodate researchers’ needs: 3 x 32, 1 x 96, and 1 x 384 assay formats for screening small numbers of test compounds, as well as custom bulk reagents for HTS applications. Assay systems are all inclusive, providing reporter cells, optimized growth media, media for diluting test compounds, a positive-control agonist, luciferase detection reagent, a white assay plate, a detailed protocol, and a protocol quick guide. All kits are shipped on dry ice.
FXR Reporter Cells are prepared using INDIGO’s proprietary CryoMite™ process. This cryo-preservation method yields high cell viability post-thaw, and provides the convenience of immediately dispensing healthy, division-competent reporter cells into assay plates. There is no need for intermediate spin-and-wash steps, viability determinations, or cell titer adjustments.
The principle application of this assay product is in the screening of test samples to quantify functional activities, either agonist or antagonist, that they may exert against the human farnesoid x receptor. This kit product is an all-inclusive assay system that includes, in addition to FXR Reporter Cells, two optimized media for use during cell culture and (optionally) in diluting the test samples, a reference agonist, Luciferase Detection Reagent, a cell culture-ready assay plate, and a detailed protocol.Assay Kit & Platforms
|Product Family||Product Number||Product Description|
|IB0060 FXR (NR1H4)||IB00601-32||Human FXR Reporter Assay System, 3 x 32 assays in 96-well format|
|IB00601||Human FXR Reporter Assay System, 1 x 96-well format assays|
|IB00602||Human FXR Reporter Assay System, 1 x 384-well format assays|
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.
Characterization of EDP-305, a Highly Potent and Selective Farnesoid X Receptor Agonist, for the Treatment of Non-alcoholic Steatohepatitis
ABSTRACT Non-alcoholic steatohepatitis (NASH), characterized by hepatocyte injury, inflammation, and fibrosis, is the maincause of chronic liver disease in the Western world. There are currently no approved pharmacological therapies for NASH,underscoring the urgent need for effective treatments. The farnesoid X receptor (FXR) has emerged as an attractive target for the treatment of metabolic and chronic
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
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
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
View Full Size Research conducted by: Jerry Thompson (1), Jun Zhang (1), & Jack Vanden Huevel (1,2) (1) Center for Nutrigenomics, Penn State University, University Park, PA 16802, USA (2) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA Date of Publication: March 2010
ABSTRACT FXR is a nuclear receptor that has gained a great deal of interest in terms of its biological role and potential as therapeutic target. Activating FXR increases transcription of genes that are geared toward preventing synthesis and uptake and promoting excretion of bile acids. One effect of FXR activation is decreased expression of Cyp7A1