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BioAssay: AID 720516

qHTS assay for small molecules that induce genotoxicity in human embryonic kidney cells expressing luciferase-tagged ATAD5: Summary

As cancer cells divide rapidly and during every cell division they need to duplicate their genome by DNA replication. The failure to do so results in the cancer cell death. Based on this concept, many chemotherapeutic agents were developed but have limitations such as low efficacy and severe side effects etc. A new cell based assay was developed to find the compounds that effectively block DNA replication either by directly damaging DNA or by inhibiting other cellular mechanisms. ..more
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 Tested Compounds
 Tested Compounds
All(8110)
 
 
Active(292)
 
 
Inactive(7497)
 
 
Inconclusive(462)
 
 
 Tested Substances
 Tested Substances
All(10486)
 
 
Active(373)
 
 
Inactive(9591)
 
 
Inconclusive(522)
 
 
AID: 720516
Data Source: Tox21 (ELG271)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-07-17
Modify Date: 2014-08-20

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 292
Related Experiments
AIDNameTypeComment
651632qHTS assay for small molecules that induce genotoxicity in human embryonic kidney cells expressing luciferase-tagged ATAD5Confirmatorydepositor-specified cross reference: ATAD5 activation screen
651634qHTS assay for small molecules that induce genotoxicity in human embryonic kidney cells expressing luciferase-tagged ATAD5 - cell viabilityConfirmatorydepositor-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:

As cancer cells divide rapidly and during every cell division they need to duplicate their genome by DNA replication. The failure to do so results in the cancer cell death. Based on this concept, many chemotherapeutic agents were developed but have limitations such as low efficacy and severe side effects etc. A new cell based assay was developed to find the compounds that effectively block DNA replication either by directly damaging DNA or by inhibiting other cellular mechanisms.

Enhanced Level of Genome Instability Gene 1 (ELG1; human ATAD5) protein levels increase in response to various types of DNA damage. Using a luciferase reporter-gene tagged with ATAD5, a cell-based assay [developed by Kyungjae Myung, NHGRI, NIH] was used to measure the induction of ATAD5 in human embryonic kidney cells (HEK293T). So, increase in luciferase activity can be used to identify the compounds that cause genetic stress. In addition to genotoxicity, these cells were also used to test for cytotoxicity by measuring the protease activity within live cells.
Protocol
Please refer to other AIDs 651632 and 651634 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 ATAD5 assay (AID 651632) and cell viability counter screen (AID 651634). 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 ATAD5 readout and the cell viability counter screen.String
2ATAD5 ActivityType of compound activity in the ATAD5 screen.String
3ATAD5 Potency (uM)*The concentration of sample yielding half-maximal activation of ATAD5.FloatμM
4ATAD5 Efficacy (%)Percent activation of ATAD5.Float%
5Viability ActivityType of compound activity in the cell viability counter screen.String
6Viability Potency (uM)The concentration of sample yielding half-maximal inhibition of cell viability.FloatμM
7Viability Efficacy (%)Percent inhibition of cell viability.Float%
8Sample SourceWhere sample was obtained.String

* Activity Concentration.

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