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BioAssay: AID 651820

qHTS Assay for Inhibitors of Hepatitis C Virus (HCV)

Hepatitis C virus (HCV) infects about 200 million people in the world. Many infected people progress to chronic liver disease including cirrhosis with a risk of developing liver cancer. To date, there is no effective vaccine for hepatitis C. Current therapy based on interferon is only effective in about half of the patients and is associated with significant adverse effects. The fraction of more ..
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 Tested Compounds
 Tested Compounds
All(339561)
 
 
Active(11624)
 
 
Inactive(268634)
 
 
Inconclusive(60309)
 
 
 Tested Substances
 Tested Substances
All(343600)
 
 
Active(11664)
 
 
Inactive(271341)
 
 
Inconclusive(60595)
 
 
 Related BioAssays
 Related BioAssays
AID: 651820
Data Source: NCGC (HCV100)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-11-28

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 11624
Related Experiments
AIDNameTypeComment
651831qHTS Assay for Inhibitors of Hepatitis C Virus (HCV): SummarySummarydepositor-specified cross reference
720575qHTS Assay for Inhibitors of Hepatitis C Virus (HCV): Confirmation Assay for Cherry-picked CompoundsConfirmatorydepositor-specified cross reference
720576qHTS Assay for Inhibitors of Hepatitis C Virus (HCV): Cytotoxicity Counterscreen for Cherry-picked CompoundsConfirmatorydepositor-specified cross reference
Description:
Hepatitis C virus (HCV) infects about 200 million people in the world. Many infected people progress to chronic liver disease including cirrhosis with a risk of developing liver cancer. To date, there is no effective vaccine for hepatitis C. Current therapy based on interferon is only effective in about half of the patients and is associated with significant adverse effects. The fraction of people with HCV who can complete a successful treatment is estimated to be no more than 10 percent. Recent development of direct-acting antivirals against HCV, such as protease and polymerase inhibitors, is promising but still requires combination with peginterferon and ribavirin for maximal efficacy. In addition, these agents are associated with high rate of resistance and many have significant side effects.

Due to the lack of a culture system for infectious HCV, the search for new HCV drugs has been greatly hampered. Cell-based screen for HCV inhibitors in use today is based on the HCV replicon system, which only targets the RNA replication step of the viral lifecycle and does not encompass viral entry, processing, assembly and secretion. High-throughput screening (HTS) with an infectious HCV system would cover the complete spectrum of potentially druggable targets in all stages of HCV lifecycle, and would have more biological relevance than other cell-based assays. Moreover, targeting several key processes in the viral life cycle may not only increase antiviral efficacy; more importantly, it may also reduce the capacity of the virus to develop resistance to the compound.

The goal of this project is to identify novel HCV inhibitors as new therapies for hepatitis C, using a highly sensitive and specific assay platform which is based on a HCV infectious cell culture system established in the laboratory and adapted for high-throughput HCV drug screen.

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

MLPCN Grant: MH095511
Assay Submitter (PI): Jake Liang, NIDDK
Protocol
The assay will start with plating 1,000 cells/well in 3 muL volume and culture for 4 h. Then 23 nL of compounds from the library collection will be added to each well, followed by adding 2.5 muL of HCVcc-Cre virus (~ 0.5 moi) and further cultured for 44 h before the luciferase assay. A volume of 4.5 muL luciferase substrates will be added to each well and the plates will be incubated at room temperature for 15 min. and then read for 15 sec. for the luciferase activity
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
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML391
PubChem Substance ID (SID) for probe 1: 161004422
PubChem Compound ID (CID) for probe 1: 70789640
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 14
Target for probe 1: HCV Luc Reporter Assay
Disease relevance for probe 1: Infections
Anti-target for probe 1: Huh 7.5.1 Cytotoxicity Assay
Fold selectivity for probe 1: 1007
Grant number for probe 1: 1R03MH095511
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 0.267 uM (0.267468μM**)% Activity at given concentration.Float%
16Activity at 0.335 uM (0.334893μM**)% Activity at given concentration.Float%
17Activity at 0.465 uM (0.465μM**)% Activity at given concentration.Float%
18Activity at 0.478 uM (0.478487μM**)% Activity at given concentration.Float%
19Activity at 0.669 uM (0.669μM**)% Activity at given concentration.Float%
20Activity at 1.170 uM (1.17μM**)% Activity at given concentration.Float%
21Activity at 1.435 uM (1.43478μM**)% Activity at given concentration.Float%
22Activity at 1.670 uM (1.66953μM**)% Activity at given concentration.Float%
23Activity at 2.373 uM (2.3731μM**)% Activity at given concentration.Float%
24Activity at 3.350 uM (3.35μM**)% Activity at given concentration.Float%
25Activity at 5.860 uM (5.86μM**)% Activity at given concentration.Float%
26Activity at 7.540 uM (7.54023μM**)% Activity at given concentration.Float%
27Activity at 8.371 uM (8.3715μM**)% Activity at given concentration.Float%
28Activity at 11.86 uM (11.8649μM**)% Activity at given concentration.Float%
29Activity at 16.70 uM (16.7μM**)% Activity at given concentration.Float%
30Activity at 29.30 uM (29.3μM**)% Activity at given concentration.Float%
31Activity at 38.15 uM (38.1525μM**)% Activity at given concentration.Float%
32Activity at 41.81 uM (41.8106μM**)% Activity at given concentration.Float%
33Activity at 59.29 uM (59.2937μM**)% Activity at given concentration.Float%
34Activity at 83.70 uM (83.7μM**)% Activity at given concentration.Float%
35Compound QCNCGC designation for data stage: 'qHTS', 'qHTS Verification', 'Secondary Profiling'String

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: MH095511

Data Table (Concise)
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