qHTS assay to identify small molecule agonists of the farnesoid-X-receptor (FXR) signaling pathway: Summary
The farnesoid-X-receptor (FXR), a nuclear hormone receptor, is highly expressed in liver, intestine, kidney and adrenal cortex. Natural ligands of FXR are the bile acids (Cholic acid, Chenodeoxy cholic acid etc). FXR is an important regulator of diverse metabolic pathways, including the bile acid homeostasis, lipid and glucose metabolisms. FXR regulates the expression of target genes by binding more ..
BioActive Compounds: 107
U.S. Tox21 Program
National Center for Advancing Translational Sciences [NCATS]
NIH Chemical Genomics Center [NCGC]
U.S. Environmental Protection Agency [EPA]
National Institutes of Environmental Health Sciences [NIEHS]
National Toxicology Program [NTP]
U.S. Food and Drug Administration [FDA]
Tox21 Assay Overview:
The farnesoid-X-receptor (FXR), a nuclear hormone receptor, is highly expressed in liver, intestine, kidney and adrenal cortex. Natural ligands of FXR are the bile acids (Cholic acid, Chenodeoxy cholic acid etc). FXR is an important regulator of diverse metabolic pathways, including the bile acid homeostasis, lipid and glucose metabolisms. FXR regulates the expression of target genes by binding either as a monomer or as a heterodimer with the retinoid X receptor (RXR). Numerous studies have reported that FXR exerts protective function during cholestasis, diabetes, liver regeneration, and cancer. To identify compounds that activate FXR signaling, GeneBLAzer FXR-UAS-bla HEK 293T cell line (Invitrogen, Carlsbad, CA) containing a beta-lactamase reporter gene under the control of a UAS response element was used to screen the Tox21 10K compound library. The cytotoxicity of the Tox21 compound library against the FXR-bla cell line was tested in parallel by measuring the cell viability using CellTiter-Glo assay (Promega, Madison, WI) in the same wells. The compounds were also tested for auto fluorescence that may interfere with the biological target readout resulting in potential false positives and/or negatives.
Please refer to other AIDs 743220, 743218, 720687, 720685, 720678 and 720681, for detailed assay protocols.
This summary is written for the purposes of summarizing the compound activities from the project combining the results from both the FXR agonist mode assay (AID 743220), cell viability counter screen (AID 743218), and auto fluorescence counter screens (AIDs 720687, 720685, 720678 and 720681). For all inactive compounds, PUBCHEM_ACTIVITY_SCORE is 0. Active compounds have PUBCHEM_ACTIVITY_SCORE between 40 and 100. Potency and efficacy were used for determining relative score. Inconclusive compounds have PUBCHEM_ACTIVITY_SCORE between 5 and 30 determined by phenotype.
Although all reasonable efforts have been made to ensure the accuracy and reliability of the data, caution should be exercised when interpreting the results as artifacts are possible from nonspecific effects such as assay signal interference. The curve fitting and activity calls presented here are based on the NCATS analysis methods. Alternative analysis methods and interpretations of the data are available at EPA (http://actor.epa.gov) and NTP (http://tools.niehs.nih.gov/cebs3/ui/).
* Activity Concentration.
Data Table (Concise)