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BioAssay: AID 743266

qHTS of PTHR Inhibitors: Primary Screen

The goal of the proposed studies is to discover new compounds that act as potent agonists on the parathyroid hormone receptor type-1 (PTHR1). The PTHR1 plays critical roles in maintaining blood calcium and phosphate levels, as well as in controlling bone remodeling. PTHR1 agonists could thus be useful for treating diseases such as hypoparathyroidism and osteoporosis. In the former disease, an more ..
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 Tested Compounds
 Tested Compounds
All(405676)
 
 
Active(308)
 
 
Inactive(398805)
 
 
Inconclusive(6685)
 
 
 Tested Substances
 Tested Substances
All(408917)
 
 
Active(308)
 
 
Inactive(401922)
 
 
Inconclusive(6687)
 
 
 Related BioAssays
 Related BioAssays
AID: 743266
Data Source: NCGC (pthr-p1)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2014-01-28
Modify Date: 2014-01-30

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 308
Related Experiments
AIDNameTypeComment
743265qHTS of PTHR Inhibitors: SummarySummarydepositor-specified cross reference
Description:
The goal of the proposed studies is to discover new compounds that act as potent agonists on the parathyroid hormone receptor type-1 (PTHR1). The PTHR1 plays critical roles in maintaining blood calcium and phosphate levels, as well as in controlling bone remodeling. PTHR1 agonists could thus be useful for treating diseases such as hypoparathyroidism and osteoporosis. In the former disease, an agonist drug would help maintain normal blood calcium and phosphate levels under conditions of parathyroid hormone deficiency. In the latter disease, an agonist drug would stimulate new bone formation and thus reduce the risk of fracture, under conditions of bone fragility, as occurs in aging.

To that end, we performed a quantitative high-throughput screening (qHTS) of the Molecular Libraries Probe Centers Network (MLPCN) compound libraries at the NIH Chemical Genomics Center (NCGC) for the parathyroid hormone receptor type-1 (PTHR1) using a unique HEK-293-derived cell line (GP2) that expresses the PTHR1 and a glosensor cAMP reporter construct.

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

MLPCN Grant: DK011794
Assay Submitter (PI): Thomas Gardella, Massachusetts General Hospital
Protocol
4 microL are dispensed into a 1536-well micro plate to yield 3,000 cells/well. The plates are then incubated overnight, after which 4 microL of 0.5 mM of BIoTium Luciferin plus 0.5 mM IBMX are added. They are then incubated at 37 degree for one hour before 23 nL of compounds are added through pinning and then incubated at 37 degree again for another hour. After the plates are kept at room temperature for 15 min before they are read on the ViewLux to measure luminescence.
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 PubChem:
Assay Cell Type: HEK293
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 0.0009732759 uM (0.000973276μM**)% Activity at given concentration.Float%
16Activity at 0.00195 uM (0.00194655μM**)% Activity at given concentration.Float%
17Activity at 0.00292 uM (0.00291983μM**)% Activity at given concentration.Float%
18Activity at 0.00584 uM (0.00583966μM**)% Activity at given concentration.Float%
19Activity at 0.00876 uM (0.00875954μM**)% Activity at given concentration.Float%
20Activity at 0.018 uM (0.0175191μM**)% Activity at given concentration.Float%
21Activity at 0.026 uM (0.0262786μM**)% Activity at given concentration.Float%
22Activity at 0.053 uM (0.0525571μM**)% Activity at given concentration.Float%
23Activity at 0.079 uM (0.0788357μM**)% Activity at given concentration.Float%
24Activity at 0.158 uM (0.157671μM**)% Activity at given concentration.Float%
25Activity at 0.237 uM (0.236507μM**)% Activity at given concentration.Float%
26Activity at 0.469 uM (0.46934μM**)% Activity at given concentration.Float%
27Activity at 0.710 uM (0.709522μM**)% Activity at given concentration.Float%
28Activity at 1.330 uM (1.32965μM**)% Activity at given concentration.Float%
29Activity at 2.253 uM (2.25319μM**)% Activity at given concentration.Float%
30Activity at 4.257 uM (4.25713μM**)% Activity at given concentration.Float%
31Activity at 6.386 uM (6.3857μM**)% Activity at given concentration.Float%
32Activity at 11.79 uM (11.7903μM**)% Activity at given concentration.Float%
33Activity at 19.16 uM (19.1571μM**)% Activity at given concentration.Float%
34Activity at 38.31 uM (38.3142μM**)% Activity at given concentration.Float%
35Activity at 57.49 uM (57.4932μM**)% Activity at given concentration.Float%
36Activity at 114.9 uM (114.943μM**)% Activity at given concentration.Float%
37Activity at 115.0 uM (115μM**)% Activity at given concentration.Float%
38Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: DK011794

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