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BioAssay: AID 743240

qHTS assay to identify small molecule antagonists 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(7337)
 
 
Active(231)
 
 
Inactive(6186)
 
 
Inconclusive(1159)
 
 
 Tested Substances
 Tested Substances
All(9305)
 
 
Active(255)
 
 
Inactive(7716)
 
 
Inconclusive(1334)
 
 
AID: 743240
Data Source: Tox21 (FXRN519)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-12-23
Modify Date: 2014-08-21

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 231
Related Experiments
AIDNameTypeComment
743217qHTS assay to identify small molecule antagonists of the farnesoid-X-receptor (FXR) signaling pathwayConfirmatorydepositor-specified cross reference: FXR antagonist mode screen
743221qHTS assay to identify small molecule antagonists of the farnesoid-X-receptor (FXR) signaling pathway - cell viability counter screenConfirmatorydepositor-specified cross reference: Cell viability counter 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 inhibit 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 in the same wells.
Protocol
Please refer to other AIDs, 743217 and 743221, 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 antagonist mode assay (AID 743217) and cell viability counter screen (AID 743221). 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
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Activity SummaryType of compound activity based on both the FXR antagonist mode screen and the cell viability counter screens.String
2Ratio ActivityType of compound activity in the ratio readout of the FXR antagonist mode screen.String
3Ratio Potency (uM)The concentration of sample yielding half-maximal inhibition in the ratio readout of the FXR antagonist mode screen.FloatμM
4Ratio Efficacy (%)Percent inhibition in the ratio readout of the FXR antagonist mode screen.Float%
5530 nm ActivityType of compound activity in the 530 nm readout of the FXR antagonist mode screen.String
6530 nm Potency (uM)The concentration of sample yielding half-maximal inhibition in the 530 nm readout of the FXR antagonist mode screen.FloatμM
7530 nm Efficacy (%)Percent inhibition in the 530 nm readout of the FXR antagonist mode screen.Float%
8460 nm ActivityType of compound activity in the 460 nm readout of the FXR antagonist mode screen.String
9460 nm Potency (uM)The concentration of sample yielding half-maximal inhibition in the 460 nm readout of the FXR antagonist mode screen.FloatμM
10460 nm Efficacy (%)Percent inhibition in the 460 nm readout of the FXR antagonist mode screen.Float%
11Viability ActivityType of compound activity in the cell viability counter screens.String
12Viability Potency (uM)The concentration of sample yielding half-maximal inhibition in the cell viability counter screen.FloatμM
13Viability Efficacy (%)Percent inhibition in the cell viability counter screen.Float%
14Sample SourceWhere sample was obtained.String

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