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BioAssay: AID 720637

qHTS assay for small molecule disruptors of the mitochondrial membrane potential: Summary

Mitochondrial membrane potential (MMP), one of the parameters for mitochondrial function, is generated by mitochondrial electron transport chain that creates an electrochemical gradient by a series of redox reactions. This gradient drives the synthesis of ATP, a crucial molecule for various cellular processes. Measuring MMP in living cells is commonly used to assess the effect of chemicals on mitochondrial function; decreases in MMP can be detected using lipophilic cationic fluorescent dyes. ..more
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 Tested Compounds
 Tested Compounds
All(8119)
 
 
Active(1010)
 
 
Inactive(5461)
 
 
Inconclusive(2160)
 
 
 Tested Substances
 Tested Substances
All(10486)
 
 
Active(1260)
 
 
Inactive(6810)
 
 
Inconclusive(2416)
 
 
 Related BioAssays
 Related BioAssays
AID: 720637
Data Source: Tox21 (MMP146)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-09-11
Modify Date: 2014-08-20

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 1010
Related Experiments
AIDNameTypeComment
720634qHTS assay for small molecule disruptors of the mitochondrial membrane potential - cell viabilityConfirmatorydepositor-specified cross reference: Cell viability counter screen
720635qHTS assay for small molecule disruptors of the mitochondrial membrane potentialConfirmatorydepositor-specified cross reference: Mitochondrial membrane potential 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:

Mitochondrial membrane potential (MMP), one of the parameters for mitochondrial function, is generated by mitochondrial electron transport chain that creates an electrochemical gradient by a series of redox reactions. This gradient drives the synthesis of ATP, a crucial molecule for various cellular processes. Measuring MMP in living cells is commonly used to assess the effect of chemicals on mitochondrial function; decreases in MMP can be detected using lipophilic cationic fluorescent dyes.

A homogenous cell-based assay with a water soluble mitochondrial membrane potential sensor (m-MPI, Codex Biosolutions, MD) was used to evaluate chemically induced mitochondrial toxicity. The dye accumulates in the mitochondria of healthy cells as aggregates, with red fluorescence. The mitochondrial potential decreases and the dye could not accumulate in the mitochondria and remains in the cytoplasm in monomers, with green fluorescence. In addition to the mitochondrial potential assay, these cells were also used to test the cytotoxicity by determining the cell viability in the culture based on the quantitation of ATP present. The cytotoxicity was measured in the same assay well of MMP assay.
Protocol
Please refer to other AIDs 720635, and 720634, 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 mitochondrial membrane potential assay (AID 720635) and cell viability counter screen (AID 720634). 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 MMP readout and the cell viability counter screen.String
2Ratio ActivityType of compound activity in the ratio readout of the MMP screen.String
3Ratio Potency (uM)*The concentration of sample yielding half-maximal activation in the ratio readout of the MMP screen.FloatμM
4Ratio Efficacy (%)Percent activation in the ratio readout of the MMP screen.Float%
5535 nm ActivityType of compound activity in the 535 nm readout of the MMP screen.String
6535 nm Potency (uM)he concentration of sample yielding half-maximal activation in the 535 nm readout of the MMP screen.FloatμM
7535 nm Efficacy (%)Type of compound activity in the 535 nm readout of the MMP screen.Float%
8590 nm ActivityType of compound activity in the 590 nm readout of the MMP screen.String
9590 nm Potency (uM)he concentration of sample yielding half-maximal activation in the 590 nm readout of the MMP screen.FloatμM
10590 nm Efficacy (%)Type of compound activity in the 590 nm readout of the MMP screen.Float%
11Viability ActivityType of compound activity in the cell viability counter screen.String
12Viability Potency (uM)The concentration of sample yielding half-maximal inhibition of cell viability.FloatμM
13Viability Efficacy (%)Percent inhibition of cell viability.Float%
14Sample SourceWhere sample was obtained.String

* Activity Concentration.

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