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BioAssay: AID 651644

qHTS Assay for Inhibitors of the HIV-1 protein Vpr

Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, contains a protein called viral protein R (Vpr) that plays an important role in the viral life cycle and the pathogenesis of HIV-1. ..more
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 Tested Compounds
 Tested Compounds
All(361865)
 
 
Active(750)
 
 
Inactive(353990)
 
 
Inconclusive(7146)
 
 
 Tested Substances
 Tested Substances
All(362225)
 
 
Active(751)
 
 
Inactive(354320)
 
 
Inconclusive(7154)
 
 
AID: 651644
Data Source: NCGC (VPR001)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-10-16

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 750
Related Experiments
AIDNameTypeComment
651643qHTS Assay for Inhibitors of the HIV-1 protein Vpr: SummarySummarydepositor-specified cross reference
Description:
Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, contains a protein called viral protein R (Vpr) that plays an important role in the viral life cycle and the pathogenesis of HIV-1.

Vpr plays multiple roles during the viral life cycle and displays several distinct activities in host cells. These Vpr specific activities include cytoplasmic-nuclear shuttling, induction of cell cycle G2 arrest and cell killing. The cytoplasmic-nuclear shuttling is believed to participate in nuclear transport of the proviral integration complex (PIC). The cell cycle G2 arrest induced by Vpr is thought to suppress human immune functions by preventing T cell clonal expansion and to provide an optimized cellular environment for maximal levels of viral replication. In addition, Vpr induces apoptosis, which may contribute to the depletion of CD4 T cells in HIV-infected patients. Since the Vpr-specific activities have been linked to such clinical manifestation of AIDS as activation of viral replication, suppression of host immune responses and depletion of CD4+ T-lymphocytes, identification of new molecular probes that can inhibit the Vpr activities could potentially provide a new approach to reduce Vpr-mediated detrimental effects in HIV-infected patients, and thus prolong patient's lives. Currently, there are no anti-Vpr drugs.
A fission yeast (Schizosaccharomyces pombe) model system for the Vpr studies has been developed which measures HIV-1 Vpr-induced cell death. This assay will be used for to screen the NIH Molecular Libraries Small Molecule Repository (MLSMR) identify small molecule HIV-1 Vpr inhibitors.

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

MLPCN Grant: NS063880
Assay Submitter (PI): Richard Zhao, University of Maryland
Protocol
The fission yeast RE007 strain was used, which carries a single integrated copy of HIV-1 vpr gene in the yeast chromosome. The starting culture was frozen stock 100ul of yeast RE007 in 150ml of *PMG+AL medium, Incubation in 30 degree plus 99% humidity for 18 hours. Next day dispensed 2.5ul of PMG+AL medium in each well to 1536 well white solid plate, then 23nL compound were delivered to each well using a pin tool. Check OD for overnight culture and add cell density at 0.01 for each well, incubation in 30 degree plus 99% humidity for 24 hours. After add 5 ul of *BacTiter/Glo detect reagent to each well at room temperature for 5 minutes then to red out results with Viewlux CCD camera.
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 inhibitors are ranked higher than compounds that showed apparent activation.
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
Show more
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 0.184 uM (0.184μM**)% Activity at given concentration.Float%
16Activity at 0.369 uM (0.369μM**)% Activity at given concentration.Float%
17Activity at 0.516 uM (0.516μM**)% Activity at given concentration.Float%
18Activity at 0.674 uM (0.674269μM**)% Activity at given concentration.Float%
19Activity at 0.737 uM (0.737136μM**)% Activity at given concentration.Float%
20Activity at 1.033 uM (1.03287μM**)% Activity at given concentration.Float%
21Activity at 1.470 uM (1.47μM**)% Activity at given concentration.Float%
22Activity at 1.840 uM (1.84μM**)% Activity at given concentration.Float%
23Activity at 2.580 uM (2.58μM**)% Activity at given concentration.Float%
24Activity at 3.689 uM (3.68924μM**)% Activity at given concentration.Float%
25Activity at 4.235 uM (4.2347μM**)% Activity at given concentration.Float%
26Activity at 5.175 uM (5.17453μM**)% Activity at given concentration.Float%
27Activity at 7.370 uM (7.37μM**)% Activity at given concentration.Float%
28Activity at 9.220 uM (9.22μM**)% Activity at given concentration.Float%
29Activity at 12.90 uM (12.9μM**)% Activity at given concentration.Float%
30Activity at 18.40 uM (18.397μM**)% Activity at given concentration.Float%
31Activity at 25.37 uM (25.3661μM**)% Activity at given concentration.Float%
32Activity at 37.51 uM (37.5059μM**)% Activity at given concentration.Float%
33Activity at 73.70 uM (73.7041μM**)% Activity at given concentration.Float%
34Activity at 92.19 uM (92.1938μM**)% Activity at given concentration.Float%
35Activity at 129.4 uM (129.388μM**)% Activity at given concentration.Float%
36Activity at 184.0 uM (184μM**)% Activity at given concentration.Float%
37Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: NS063880

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