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BioAssay: AID 651751

qHTS assay for small molecule activators of the rat pregnane X receptor (rPXR) signaling pathway

The Pregnane X receptor (PXR), a ligand activated nuclear receptor plays a critical role in the regulation of genes involved in drug metabolism and transporters. PXR binds xenobiotics and when compounds interact with PXR produces enhanced expression of CYP3A genes. In humans PXR activation and CYP3A4 induction can be problematic due to their interactions with co-medicated drugs and decrease their more ..
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 Tested Compounds
 Tested Compounds
All(2329)
 
 
Active(129)
 
 
Inactive(2046)
 
 
Inconclusive(202)
 
 
 Tested Substances
 Tested Substances
All(2864)
 
 
Active(152)
 
 
Inactive(2486)
 
 
Inconclusive(226)
 
 
 Related BioAssays
 Related BioAssays
AID: 651751
Data Source: NCGC (PXR613)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Other
Deposit Date: 2012-11-05

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 129
Description:
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]

Assay overview:

The Pregnane X receptor (PXR), a ligand activated nuclear receptor plays a critical role in the regulation of genes involved in drug metabolism and transporters. PXR binds xenobiotics and when compounds interact with PXR produces enhanced expression of CYP3A genes. In humans PXR activation and CYP3A4 induction can be problematic due to their interactions with co-medicated drugs and decrease their efficacy or increase their own metabolism. However, there are known species-specific differences with regard to PXR activation that should be taken into account when animal PXR data are extrapolated to humans. A cell based rat PXR (rPXR) assay (developed by Puracyp, Inc., CA) was used to assess the activation of rPXR.
Protocol
Assay Protocol Summary:

2,000 rPXR cells were dispensed at 5 uL/well in the white, solid-bottom 1536-well plates using a Multidrop Combi (Thermo Scientific) dispenser. Following transfer of 23 nL compound or DMSO vehicle by a pin tool, the plates were incubated 24 hr at 37 C and 5% CO2. 5 ul One-Glo (Promega) was then added to each plate and following 30 min incubation at room temperature, luciferase activity was quantified on a ViewLux CCD-based plate reader.
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 0.0005215015 uM (0.000521501μM**)% Activity at given concentration.Float%
16Activity at 0.00156 uM (0.0015582μM**)% Activity at given concentration.Float%
17Activity at 0.00466 uM (0.00465609μM**)% Activity at given concentration.Float%
18Activity at 0.00590 uM (0.00589862μM**)% Activity at given concentration.Float%
19Activity at 0.014 uM (0.0140533μM**)% Activity at given concentration.Float%
20Activity at 0.042 uM (0.0417583μM**)% Activity at given concentration.Float%
21Activity at 0.068 uM (0.0684607μM**)% Activity at given concentration.Float%
22Activity at 0.127 uM (0.126926μM**)% Activity at given concentration.Float%
23Activity at 0.378 uM (0.378213μM**)% Activity at given concentration.Float%
24Activity at 0.782 uM (0.781506μM**)% Activity at given concentration.Float%
25Activity at 1.156 uM (1.15581μM**)% Activity at given concentration.Float%
26Activity at 3.420 uM (3.41952μM**)% Activity at given concentration.Float%
27Activity at 5.843 uM (5.84271μM**)% Activity at given concentration.Float%
28Activity at 10.21 uM (10.2119μM**)% Activity at given concentration.Float%
29Activity at 30.24 uM (30.2438μM**)% Activity at given concentration.Float%
30Activity at 43.68 uM (43.6833μM**)% Activity at given concentration.Float%
31Activity at 92.27 uM (92.2654μM**)% Activity at given concentration.Float%
32Activity at 218.9 uM (218.934μM**)% Activity at given concentration.Float%
33Activity at 489.4 uM (489.435μM**)% Activity at given concentration.Float%
34Activity at 1094.5 uM (1094.55μM**)% Activity at given concentration.Float%
35Activity at 2447.4 uM (2447.39μM**)% Activity at given concentration.Float%
36Activity at 5811.1 uM (5811.06μM**)% Activity at given concentration.Float%
37Activity at 12995.4 uM (12995.4μM**)% Activity at given concentration.Float%
38Activity at 29059.9 uM (29059.9μM**)% Activity at given concentration.Float%
39Activity at 64977.0 uM (64977μM**)% Activity at given concentration.Float%
40Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.

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