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BioAssay: AID 652104

qHTS of TDP-43 Inhibitors

The goal of this project is to identify new chemical probes capable of reversing the toxicity associated with TDP-43 which is associated with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. These compounds will provide a complementary approach to deciphering the tangled mechanisms of toxicity and protection that we have uncovered through genome-wide genetic screens and are beginning to uncover in a large-scale proteomics analysis with mass spectroscopy. ..more
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 Tested Compounds
 Tested Compounds
All(403694)
 
 
Active(7150)
 
 
Inactive(368751)
 
 
Inconclusive(28180)
 
 
 Tested Substances
 Tested Substances
All(406923)
 
 
Active(7165)
 
 
Inactive(371527)
 
 
Inconclusive(28231)
 
 
AID: 652104
Data Source: NCGC (TDP43100)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2013-03-14

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 7150
Related Experiments
AIDNameTypeComment
652093qHTS of TDP-43 Inhibitors: SummarySummarydepositor-specified cross reference
Description:
The goal of this project is to identify new chemical probes capable of reversing the toxicity associated with TDP-43 which is associated with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. These compounds will provide a complementary approach to deciphering the tangled mechanisms of toxicity and protection that we have uncovered through genome-wide genetic screens and are beginning to uncover in a large-scale proteomics analysis with mass spectroscopy.

To this end, a miniaturized assay was developed to be screened against the Molecular Libraries Small Molecule Repository (MLSMR) to discover TDP-43 inhibitors. Please note that in the set-up this yeast-based assay compounds that inhibit as TDP-43, have a read-out as activators.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: NS060957
Assay Submitter (PI): Susan Lindquist, Whitehead Institute/MIT
Protocol
Dispense 2.5 microL yeast galactose medium per 1536-well plate, pin compound, dispense 2.5 microL TDP-43 expressing yeast in galactose medium at OD600=0.02 (pregrown in raffinose medium to mid-log phase) per well, incubate for 24 hr at 30 deg C, and cell growth will be measured using 5 microL of Bactiter/Glo reagent to entire plate and read using Luminescence Protocol in ViewLux.
Comment
Compound Ranking:

1. Compounds are first classified as having full titration curves, partial modulation, partial curve (weaker actives), single point activity (at highest concentration only), or inactive. See data field "Curve Description". For this assay, apparent activators are ranked higher than compounds that showed apparent inhibition.
2. For all inactive compounds, PUBCHEM_ACTIVITY_SCORE is 0. For all active compounds, a score range was given for each curve class type given above. Active compounds have PUBCHEM_ACTIVITY_SCORE between 40 and 100. Inconclusive compounds have PUBCHEM_ACTIVITY_SCORE between 1 and 39. Fit_LogAC50 was used for determining relative score and was scaled to each curve class' score range.
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Functional
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1PhenotypeIndicates type of activity observed: inhibitor, activator, fluorescent, cytotoxic, inactive, or inconclusive.String
2Potency*Concentration at which compound exhibits half-maximal efficacy, AC50. Extrapolated AC50s also include the highest efficacy observed and the concentration of compound at which it was observed.FloatμM
3EfficacyMaximal efficacy of compound, reported as a percentage of control. These values are estimated based on fits of the Hill equation to the dose-response curves.Float%
4Analysis CommentAnnotation/notes on a particular compound's data or its analysis.String
5Activity_ScoreActivity score.Integer
6Curve_DescriptionA description of dose-response curve quality. A complete curve has two observed asymptotes; a partial curve may not have attained its second asymptote at the highest concentration tested. High efficacy curves exhibit efficacy greater than 80% of control. Partial efficacies are statistically significant, but below 80% of control.String
7Fit_LogAC50The logarithm of the AC50 from a fit of the data to the Hill equation (calculated based on Molar Units).Float
8Fit_HillSlopeThe Hill slope from a fit of the data to the Hill equation.Float
9Fit_R2R^2 fit value of the curve. Closer to 1.0 equates to better Hill equation fit.Float
10Fit_InfiniteActivityThe asymptotic efficacy from a fit of the data to the Hill equation.Float%
11Fit_ZeroActivityEfficacy at zero concentration of compound from a fit of the data to the Hill equation.Float%
12Fit_CurveClassNumerical encoding of curve description for the fitted Hill equation.Float
13Excluded_PointsWhich dose-response titration points were excluded from analysis based on outlier analysis. Each number represents whether a titration point was (1) or was not (0) excluded, for the titration series going from smallest to highest compound concentrations.String
14Max_ResponseMaximum activity observed for compound (usually at highest concentration tested).Float%
15Activity at 0.0007804147 uM (0.000780415μM**)% Activity at given concentration.Float%
16Activity at 0.00234 uM (0.00234124μM**)% Activity at given concentration.Float%
17Activity at 0.00702 uM (0.00702378μM**)% Activity at given concentration.Float%
18Activity at 0.021 uM (0.0210713μM**)% Activity at given concentration.Float%
19Activity at 0.063 uM (0.0632139μM**)% Activity at given concentration.Float%
20Activity at 0.190 uM (0.189642μM**)% Activity at given concentration.Float%
21Activity at 0.397 uM (0.396529μM**)% Activity at given concentration.Float%
22Activity at 1.817 uM (1.81703μM**)% Activity at given concentration.Float%
23Activity at 5.120 uM (5.12033μM**)% Activity at given concentration.Float%
24Activity at 9.220 uM (9.22μM**)% Activity at given concentration.Float%
25Activity at 15.36 uM (15.361μM**)% Activity at given concentration.Float%
26Activity at 46.08 uM (46.0829μM**)% Activity at given concentration.Float%
27Activity at 46.10 uM (46.1μM**)% Activity at given concentration.Float%
28Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: NS060957

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