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BioAssay: AID 743239

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 ..
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 Tested Compounds
 Tested Compounds
All(7343)
 
 
Active(107)
 
 
Inactive(6898)
 
 
Inconclusive(449)
 
 
 Tested Substances
 Tested Substances
All(9315)
 
 
Active(118)
 
 
Inactive(8705)
 
 
Inconclusive(492)
 
 
AID: 743239
Data Source: Tox21 (FXRA272)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: Other
Deposit Date: 2013-12-23
Modify Date: 2014-08-14

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 107
Related Experiments
AIDNameTypeComment
720678qHTS assay to test for compound auto fluorescence at 460 nm (blue) in HEK293 cellsConfirmatorydepositor-specified cross reference: Blue (460 nm) auto fluorescence counter screen in HEK293 cells
720681qHTS assay to test for compound auto fluorescence at 460 nm (blue) in HEK293 cell free cultureConfirmatorydepositor-specified cross reference: Blue (460 nm) auto fluorescence counter screen in HEK293 cell free culture
720685qHTS assay to test for compound auto fluorescence at 460 nm (blue) in HepG2 cell free cultureConfirmatorydepositor-specified cross reference: Blue (460 nm) auto fluorescence counter screen in HepG2 cell free culture
720687qHTS assay to test for compound auto fluorescence at 460 nm (blue) in HepG2 cellsConfirmatorydepositor-specified cross reference: Blue (460 nm) auto fluorescence counter screen in HepG2 cells
743218qHTS assay to identify small molecule agonists of the farnesoid-X-receptor (FXR) signaling pathway - cell viability counter screenConfirmatorydepositor-specified cross reference: Cell viability counter screen
743220qHTS assay to identify small molecule agonists of the farnesoid-X-receptor (FXR) signaling pathwayConfirmatorydepositor-specified cross reference: FXR agonist mode screen
Description:
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.
Protocol
Please refer to other AIDs 743220, 743218, 720687, 720685, 720678 and 720681, for detailed assay protocols.
Comment
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.

Disclaimer:

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/).
Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Activity SummaryType of compound activity based on both the FXR agonist mode screen and the cell viability and auto fluorescence counter screens.String
2Ratio ActivityType of compound activity in the ratio readout of the FXR agonist mode screen.String
3Ratio Potency (uM)*The concentration of sample yielding half-maximal activation in the ratio readout of the FXR agonist mode screen.FloatμM
4Ratio Efficacy (%)Percent activation in the ratio readout of the FXR agonist mode screen.Float%
5530 nm ActivityType of compound activity in the 530 nm readout of the FXR agonist mode screen.String
6530 nm Potency (uM)The concentration of sample yielding half-maximal activation in the 530 nm readout of the FXR agonist mode screen.FloatμM
7530 nm Efficacy (%)Percent activation in the 530 nm readout of the FXR agonist mode screen.Float%
8460 nm ActivityType of compound activity in the 460 nm readout of the FXR agonist mode screen.String
9460 nm Potency (uM)The concentration of sample yielding half-maximal activation in the 460 nm readout of the FXR agonist mode screen.FloatμM
10460 nm Efficacy (%)Percent activation in the 460 nm readout of the FXR agonist mode screen.Float%
11Viability ActivityType of activity in the cell viability counter screen.String
12Viability Potency (uM)The concentration of sample yielding half-maximal inhibition in the cell viability screen.FloatμM
13Viability Efficacy (%)Percent inhibition in the cell viability counter screen.Float%
14Blue (460 nm) auto fluorescence outcomeType of compound activity in the auto fluorescence counter screens.String
15Sample SourceWhere sample was obtained.String

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
Classification
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