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BioAssay: AID 652048

qHTS of D3 Dopamine Receptor Agonist: qHTS

D3 DARs represent a very important target for the treatment of several neuropsychiatric disorders. Indeed, one of the most promising therapeutic applications for the D3 DAR is in the area of addiction and related disorders. Several lines of evidence suggest that partial agonists or antagonists of the D3 DAR may be therapeutic for drug abuse and relapse. Accumulating evidence suggests that more ..
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 Tested Compounds
 Tested Compounds
All(407543)
 
 
Active(2381)
 
 
Inactive(405229)
 
 
 Tested Substances
 Tested Substances
All(412073)
 
 
Active(2394)
 
 
Inactive(409679)
 
 
AID: 652048
Data Source: NCGC (D3Ago100)
BioAssay Type: Primary, Primary Screening, Single Concentration Activity Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2013-02-21
Modify Date: 2013-03-12

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 2381
Related Experiments
AIDNameTypeComment
652050qHTS of D3 Dopamine Receptor Agonist: SummarySummarydepositor-specified cross reference
720506qHTS of D3 Dopamine Receptor Agonist: D3 Dopamine Receptor B-arrestin Agonist Confirmatory AssayConfirmatorysame project related to Summary assay
720507qHTS of D3 Dopamine Receptor Agonist: D2 Dopamine Receptor B-arrestin Agonist CounterscreenConfirmatorysame project related to Summary assay
Description:
D3 DARs represent a very important target for the treatment of several neuropsychiatric disorders. Indeed, one of the most promising therapeutic applications for the D3 DAR is in the area of addiction and related disorders. Several lines of evidence suggest that partial agonists or antagonists of the D3 DAR may be therapeutic for drug abuse and relapse. Accumulating evidence suggests that reducing D3 DAR activity may regulate the motivation to self-administer drugs and disrupt drug-associated cue-induced craving and relapse or reinstatement of drug taking. These findings have been observed with a number of addictive substances including cocaine, amphetamine, nicotine, and alcohol. It is particularly interesting that partial agonists are effective in these preclinical models, suggesting that only partial blockade of the D3 DAR is needed and may, in fact, prove to be more beneficial than full blockade. Antagonism of the D3 DAR may also be therapeutic in the treatment of schizophrenia or psychosis. Notably, while all antipsychotic drugs block the D2 DAR, they also block the D3 DAR to various degrees. Since the D3 DAR is expressed in areas of the CNS associated with the control of mood and emotion, it has been hypothesized that selective antagonism of the D3 DAR may be effective in treating psychosis without inducing the motor side effects typically seen with D2 DAR antagonists. Interestingly, D3 DAR antagonism has also been suggested to be highly beneficial in the treatment of certain motor/movement disorders such as L-DOPA-induced dyskinesias, which typically arise during late-stage Parkinson's disease treatment.

The goal of this project is to use high throughput screening approaches to identify and develop novel, highly selective small molecule allosteric modulators of the D3 DAR for use as in vitro and in vivo pharmacological tools and in proof-of-concept experiments in animal models of neuropsychiatric disease. This part of the project aims to discover novel agonist.

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

MLPCN Grant: MH094203
Assay Submitter (PI): David Sibley, NINDS
Protocol
Freshly passaged cells are plated in 1536 well white, solid bottom plates at a density of 1500 cells/well in 3microl of complete media. After an overnight incubation at 37 degrees C in 5% CO2, cells are loaded with 23nl of test compound from the compound library (as well as dopamine controls) using a 1536 pintool and incubated at 37 degrees C for 90 minutes. Two microliters of DiscoveRx reagent is then added to all cells, and they are incubated for an additional 30 - 60 minutes at room temperature. Following incubation, luminescence is measured on a ViewLux CCD-based luminometer reader using a 20 sec exposure time.
Comment
Compounds whose "max activity" is <= 30% are considered "active" and assigned a score of 90; for compounds with a "max activity" < 30% are considered "inactive" and are assigned a score of 10.
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
2PotencyConcentration 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 0.230 uM (0.23μM**)% Activity at given concentration.Float%
16Activity at 1.030 uM (1.03μM**)% Activity at given concentration.Float%
17Activity at 1.150 uM (1.15μM**)% Activity at given concentration.Float%
18Activity at 2.300 uM (2.3μM**)% Activity at given concentration.Float%
19Activity at 4.600 uM (4.59971μM**)% Activity at given concentration.Float%
20Activity at 5.158 uM (5.15753μM**)% Activity at given concentration.Float%
21Activity at 7.339 uM (7.33876μM**)% Activity at given concentration.Float%
22Activity at 11.50 uM (11.4997μM**)% Activity at given concentration.Float%
23Activity at 22.95 uM (22.9486μM**)% Activity at given concentration.Float%
24Activity at 26.25 uM (26.2521μM**)% Activity at given concentration.Float%
25Activity at 33.79 uM (33.7948μM**)% Activity at given concentration.Float%
26Activity at 38.20 uM (38.2μM**)% Activity at given concentration.Float%
27Activity at 54.63 uM (54.6251μM**)% Activity at given concentration.Float%
28Activity at 57.70 uM (57.7μM**)% Activity at given concentration.Float%
29Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

** Test Concentration.
Additional Information
Grant Number: MH094203

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