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BioAssay: AID 602425

SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal kinetic assay utilizing the direct detection of NADPH - Set 3

Tropical malaria caused by the protozoan parasite Plasmodium falciparum is responsible for up to three million deaths annually. Due to increasing regional distribution and resistances against the clinically used antimalarials, novel antimalarial drugs - which have new mechanisms of action and are suitable for combination therapies - are urgently required. Plasmodium falciparum Glucose-6-phosphate more ..
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 Tested Compounds
 Tested Compounds
All(17)
 
 
Active(12)
 
 
Inactive(5)
 
 
 Tested Substances
 Tested Substances
All(17)
 
 
Active(12)
 
 
Inactive(5)
 
 
AID: 602425
Data Source: Burnham Center for Chemical Genomics (SBCCG-A814-pfG6PDH-OK-DryPowder-Assay-3)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2012-03-20
Hold-until Date: 2012-09-28
Modify Date: 2012-09-28

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 12
Related Experiments
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AIDNameTypeComment
504690uHTS identification of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assayScreeningdepositor-specified cross reference
504696Summary Assay for small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphateSummarydepositor-specified cross reference
504753Single concentration confirmation of uHTS small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assayScreeningsame project related to Summary assay
504765Dose Response confirmation of uHTS small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assayConfirmatorysame project related to Summary assay
504792Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity Assay for Inhibitors of Plasmodium falciparum Glucose-6-Phosphate DehydrogenaseConfirmatorysame project related to Summary assay
504862uHTS Identification of Diaphorase Inhibitors and Chemical Oxidizers: Counter Screen for the uHTS identification of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay in the presence of 10 uM NADPHScreeningsame project related to Summary assay
504863uHTS Identification of Diaphorase Inhibitors and Chemical Oxidizers: Counter Screen for the uHTS identification of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay in the presence of 30 uM NADPHScreeningsame project related to Summary assay
540252Dose Response orthogonal assay utilizing the direct end-point detection of NADPH for uHTS small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenaseConfirmatorysame project related to Summary assay
540269Dose Response orthogonal kinetic assay utilizing the direct detection of NADPH for uHTS small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenaseConfirmatorysame project related to Summary assay
588414SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase using a Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity AssayConfirmatorysame project related to Summary assay
588415SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assayConfirmatorysame project related to Summary assay
588588SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal assay utilizing the direct end-point detection of NADPHConfirmatorysame project related to Summary assay
588593SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal kinetic assay utilizing the direct detection of NADPHConfirmatorysame project related to Summary assay
588671SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay - Set 2Confirmatorysame project related to Summary assay
588672SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase using a Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity Assay - Set 2Confirmatorysame project related to Summary assay
602130SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase using a Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity Assay - Set 3Confirmatorysame project related to Summary assay
602131SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay - Set 3Confirmatorysame project related to Summary assay
602132SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal assay utilizing the direct end-point detection of NADPH - Set 2Confirmatorysame project related to Summary assay
602133SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal kinetic assay utilizing the direct detection of NADPH - Set 2Confirmatorysame project related to Summary assay
602423SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay - Set 4Confirmatorysame project related to Summary assay
602424SAR analysis of small molecule inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase using a Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity Assay - Set 4Confirmatorysame project related to Summary assay
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1R21AI082434-01
Assay Provider: Lars Bode, Ph.D., University of California San Diego, San Diego, CA

Tropical malaria caused by the protozoan parasite Plasmodium falciparum is responsible for up to three million deaths annually. Due to increasing regional distribution and resistances against the clinically used antimalarials, novel antimalarial drugs - which have new mechanisms of action and are suitable for combination therapies - are urgently required. Plasmodium falciparum Glucose-6-phosphate dehydrogenase (PfGluPho) is a potential novel target for antimalarial drug design. Glucose-6-Phosphate Dehydrogenase (G6PD) reaction is the first and rate-limiting step in the pentose phosphate pathway (PPP), catalyzed by a bifunctional enzyme Plasmodium falciparum Glucose-6-phosphate dehydrogenase-6-Phosphogluconolactonase (PfGluPho) catalyzing the first two steps of the PPP, a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. Plasmodium falciparum cells and infected host RBCs rely on accelerated glucose flux and are dependent on glucose-6-phopshate dehydrogenase activity of PfGluPho. The parasite enzyme is essential for plasmodium proliferation and it differs structurally and mechanistically from the human enzyme, thus making it an excellent target for novel antimalarial drug design. Prior to this study PfGluPho protein was unavailable and its selective and specific inhibitors are non-existent. Given this gap, our rationale in developing a HTS screen is to find chemical probes that inhibit Plasmodium G6PD activity that might lead to novel anti-malarial therapies.

Glucose-6-Phosphate Dehydrogenase (G6PD), an enzyme that converts Glucose-6-Phosphate to 6-Phosphoglucono-delta-lactone, is the first and rate-limiting step of the Pentose Phosphate Pathway (PPP), one of the key pathways for glucose metabolism in most cells. The activity of G6PD determines whether glucose is metabolized through glycolysis or the PPP. In contrast to glycolysis, the primary role of the PPP is anabolic rather than catabolic, providing NADPH for the biosynthesis of fatty acids and cholesterol, as well as Ribose-5-Phosphate as the precursor for the synthesis of nucleotides and nucleic acids, which is especially important for rapidly growing plasmodium cells. Parasite and plasmodium-infected host cells demonstrate elevated rates of glucose consumption comparing to uninfected red blood cells.

The purpose of this assay is to test compounds confirmed in dose response as inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase in an orthogonal kinetic assay which utilizes the direct detection of NADPH. These compounds were originally identified in the primary screen "uHTS identification of small molecule inhibitors of Plasmodium falciparum Glucose-6-phosphate dehydrogenase via a fluorescence intensity assay", AID 504690 and to study the structure-activity relationship on analogs of the confirmed hits. Compounds are either acquired from commercial sources or synthesized internally.
The primary assay utilizes a G6PD- NADPH-coupled assay in which G6PD activity is detected through conversion of its product, glucose-6-phosphate, to 6-phosphoglucono-delta-lactone concomitant with NADP converted to NADPH. The NADPH is then detected via a resazurin-diaphorase fluorogenic reaction. The orthogonal assay presented here allows for the direct detection of NADPH formation over time, thus allowing for the discrimination of compounds that are interfering with the coupled resazurin-diaphorase reaction and not the G6PD enzyme itself.
Protocol
A. Brief Description of the Assay:
This assay measures the activity of inhibitors of the Plasmodium falciparum G6PDH enzyme via the direct detection of NADPH fluorescence.

B. Materials:
Item, Source, Cat #
pfG6PDH Enzyme Stock Solutions, Assay Provider, N/A
Glucose-6-Phosphate, Sigma-Aldrich, G7250
NADP, Amresco, 0760
Tris-HCl pH 7.5, Sigma-Aldrich, T6066
Tween 20, Sigma-Aldrich, P1379
MgCl2, Sigma-Aldrich, M1028
Bovine serum albumin, Sigma-Aldrich, A7888
Molecular Grade Water, Mediatech, 46-000-CM
1536 well black solid flat bottom Non-Binding plate, Corning, 3728

C. Procedures:
1. Prepare Reagents as described in sections D. Recipe.
2. Using LabCyte Echo, transfer varying volumes of test compound in DMSO from Echo qualified plate into assay plate Col. 5 - 48 to achieve the desired dose response concentrations and range. Backfill wells with DMSO to equilibrate DMSO concentrations. An equal volume of DMSO should be transferred to col. 1-4 for positive and negative control wells.
3. Using a Multidrop Combi, add 2.5 uL/well of Mix 1 (enzyme solution) to col. 1-48.
4. Using a Multidrop Combi, add 2.5 uL/well of Mix 2 (substrate solution) to col. 5-48 for the negative control and test compound wells.
5. Using a Multidrop Combi, add 2.5 uL/well of Mix 3 (control solution) to col. 1-4 for the positive control.
6. Spin plates at 1000 rpm for 1 minute in centrifuge.
7. Immediately read the plates at 5 minute intervals on a plate reader capable of reading fluorescence at Ex. 340 nm, Em. 450 nm.
9. Reaction rate is calculated by dividing the change in fluorescence (RFU) by time in minutes.

D. Recipe
Enzyme Solution
0.4 ug/ml pfG6PDH Enzyme (0.2 ug/ml FAC), 50 mM Tris-HCl pH 7.5. 0.005% Tween 20, 1 mg/ml BSA
Substrate Solution
40 uM G6P (20uM FAC), 6 uM NADP (3 uM FAC), 50 mM Tris-HCl pH 7.5. 0.005% Tween 20, 1 mg/ml BSA, 6.6 mM MgCl2 (3.3 mM FAC)
Control Solution
6 uM NADP (3uM FAC), 50 mM Tris-HCl pH 7.5. 0.005% Tween 20, 1 mg/ml BSA, 6.6 mM MgCl2 (3.3 mM FAC)

E. Special Note:
1. All reagents should be made up according to its spec-sheet or otherwise in Mol. Grade Water.
2. Storage conditions after reagents are made up:
Reagent, Temperature, Notes
pfG6PDH, -80 oC
G6P, -80 oC
NADP, -80 oC
Comment
The activity was measured at 5 and 35 minutes and reaction rate assumed to be linear over the tested range. The %Activity at each concentration was set equal to the reaction rate and plotted to produce the IC50 curves.

Compounds that tested with an IC50 <= 80 uM concentration are defined as actives in this assay.

To simplify the distinction between the inactives of the primary screen and of the confirmatory screening stage, the Tiered Activity Scoring System was developed and implemented. Its utilization for the pfG6PD assay is described below.

Activity Scoring
Activity scoring rules were devised to take into consideration compound efficacy, its potential interference with the assay and the screening stage that the data was obtained. Details of the Scoring System will be published elsewhere. Briefly, the outline of the scoring system utilized for the assay is as follows:

1) First tier (0-40 range) is reserved for primary screening data and is not applicable in this assay.

2) Second tier (41-80 range) is reserved for dose-response confirmation data and is not applicable in this assay

3) Third tier (81-100 range) is reserved for resynthesized true positives and their analogues
a. Inactive compounds of the confirmatory stage are assigned a score value equal 81.
b. The score is linearly correlated with a compound potency and, in addition, provides a measure of the likelihood that the compound is not an artifact based on the available information.
c. The Hill coefficient is taken as a measure of compound behavior in the assay via an additional scaling factor QC:

QC = 2.6*[exp(-0.5*nH^2) - exp(-1.5*nH^2)]

This empirical factor prorates the likelihood of target-specific compound effect vs. its non-specific behavior in the assay. This factor is based on expectation that a compound with a single mode of action that achieved equilibrium in this assay demonstrates the Hill coefficient value of 1. Compounds deviating from that behavior are penalized proportionally to the degree of their deviation.
d. Summary equation that takes into account the items discussed above is

Score = 82 + 3*(pIC50 - 3)*QC,

where pIC50 is a negative log(10) of the IC50 value expressed in mole/L concentration units. This equation results in the Score values above 85 for compounds that demonstrate high potency and predictable behavior. Compounds that are inactive in the assay or whose concentration-dependent behavior are likely to be an artifact of that assay will generally have lower Score values.
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1IC50_Mean_QualifierThis qualifier is to be used with the next TID, IC50_Mean. If the qualifier is ""="", the IC50 result equals the value in that column. If the qualifier is "">"", the IC50 result is greater than that value. If the qualifier is ""<"", the IC50 result is smaller than that valueString
2IC50_Mean*IC50 value determined using a sigmoidal dose response equationFloatμM
3IC50_Qualifier_1_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
4IC50_1_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
5Std.Err(IC50)_1_Range1Standard Error of the IC50 valueFloatμM
6nH_1_Range1Hill coefficient determined using sigmoidal dose response equationFloat
7Excluded_Points_first_point_Range1Flags to indicate which of the first dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
8% Activity at 80 uM_first_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
9% Activity at 40 uM_first_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
10% Activity at 20 uM_first_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
11% Activity at 10 uM_first_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
12% Activity at 5 uM_first_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
13% Activity at 2.5 uM_first_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
14% Activity at 1.25 uM_first_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
15% Activity at 0.625 uM_first_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
16% Activity at 0.3125 uM_first_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
17% Activity at 0.15625 uM_first_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
18Excluded_Points_second_point_Range1Flags to indicate which of the second dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
19% Activity at 80 uM_second_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
20% Activity at 40 uM_second_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
21% Activity at 20 uM_second_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
22% Activity at 10 uM_second_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
23% Activity at 5 uM_second_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
24% Activity at 2.5 uM_second_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
25% Activity at 1.25 uM_second_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
26% Activity at 0.625 uM_second_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
27% Activity at 0.3125 uM_second_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
28% Activity at 0.15625 uM_second_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
29IC50_Qualifier_2_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
30IC50_2_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
31Std.Err(IC50)_2_Range1Standard Error of the IC50 valueFloatμM
32nH_2_Range1Hill coefficient determined using sigmoidal dose response equationFloat
33Excluded_Points_third_point_Range1Flags to indicate which of the third dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
34% Activity at 80 uM_third_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
35% Activity at 40 uM_third_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
36% Activity at 20 uM_third_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
37% Activity at 10 uM_third_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
38% Activity at 5 uM_third_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
39% Activity at 2.5 uM_third_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
40% Activity at 1.25 uM_third_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
41% Activity at 0.625 uM_third_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
42% Activity at 0.3125 uM_third_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
43% Activity at 0.15625 uM_third_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
44Excluded_Points_fourth_point_Range1Flags to indicate which of the fourth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
45% Activity at 80 uM_fourth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
46% Activity at 40 uM_fourth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
47% Activity at 20 uM_fourth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
48% Activity at 10 uM_fourth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
49% Activity at 5 uM_fourth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
50% Activity at 2.5 uM_fourth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
51% Activity at 1.25 uM_fourth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
52% Activity at 0.625 uM_fourth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
53% Activity at 0.3125 uM_fourth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
54% Activity at 0.15625 uM_fourth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
55IC50_Qualifier_3_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
56IC50_3_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
57Std.Err(IC50)_3_Range1Standard Error of the IC50 valueFloatμM
58nH_3_Range1Hill coefficient determined using sigmoidal dose response equationFloat
59Excluded_Points_fifth_point_Range1Flags to indicate which of the fifth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
60% Activity at 80 uM_fifth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
61% Activity at 40 uM_fifth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
62% Activity at 20 uM_fifth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
63% Activity at 10 uM_fifth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
64% Activity at 5 uM_fifth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
65% Activity at 2.5 uM_fifth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
66% Activity at 1.25 uM_fifth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
67% Activity at 0.625 uM_fifth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
68% Activity at 0.3125 uM_fifth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
69% Activity at 0.15625 uM_fifth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
70Excluded_Points_sixth_point_Range1Flags to indicate which of the sixth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
71% Activity at 80 uM_sixth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
72% Activity at 40 uM_sixth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
73% Activity at 20 uM_sixth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
74% Activity at 10 uM_sixth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
75% Activity at 5 uM_sixth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
76% Activity at 2.5 uM_sixth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
77% Activity at 1.25 uM_sixth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
78% Activity at 0.625 uM_sixth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
79% Activity at 0.3125 uM_sixth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
80% Activity at 0.15625 uM_sixth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
81IC50_Qualifier_4_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
82IC50_4_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
83Std.Err(IC50)_4_Range1Standard Error of the IC50 valueFloatμM
84nH_4_Range1Hill coefficient determined using sigmoidal dose response equationFloat
85Excluded_Points_seventh_point_Range1Flags to indicate which of the seventh dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
86% Activity at 80 uM_seventh_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
87% Activity at 40 uM_seventh_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
88% Activity at 20 uM_seventh_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
89% Activity at 10 uM_seventh_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
90% Activity at 5 uM_seventh_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
91% Activity at 2.5 uM_seventh_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
92% Activity at 1.25 uM_seventh_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
93% Activity at 0.625 uM_seventh_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
94% Activity at 0.3125 uM_seventh_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
95% Activity at 0.15625 uM_seventh_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
96Excluded_Points_eighth_point_Range1Flags to indicate which of the eighth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
97% Activity at 80 uM_eighth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
98% Activity at 40 uM_eighth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
99% Activity at 20 uM_eighth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
100% Activity at 10 uM_eighth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
101% Activity at 5 uM_eighth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
102% Activity at 2.5 uM_eighth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
103% Activity at 1.25 uM_eighth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
104% Activity at 0.625 uM_eighth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
105% Activity at 0.3125 uM_eighth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
106% Activity at 0.15625 uM_eighth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
107IC50_Qualifier_5_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
108IC50_5_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
109Std.Err(IC50)_5_Range1Standard Error of the IC50 valueFloatμM
110nH_5_Range1Hill coefficient determined using sigmoidal dose response equationFloat
111Excluded_Points_ninth_point_Range1Flags to indicate which of the ninth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
112% Activity at 80 uM_ninth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
113% Activity at 40 uM_ninth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
114% Activity at 20 uM_ninth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
115% Activity at 10 uM_ninth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
116% Activity at 5 uM_ninth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
117% Activity at 2.5 uM_ninth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
118% Activity at 1.25 uM_ninth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
119% Activity at 0.625 uM_ninth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
120% Activity at 0.3125 uM_ninth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
121% Activity at 0.15625 uM_ninth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
122Excluded_Points_tenth_point_Range1Flags to indicate which of the tenth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
123% Activity at 80 uM_tenth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
124% Activity at 40 uM_tenth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
125% Activity at 20 uM_tenth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
126% Activity at 10 uM_tenth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
127% Activity at 5 uM_tenth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
128% Activity at 2.5 uM_tenth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
129% Activity at 1.25 uM_tenth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
130% Activity at 0.625 uM_tenth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
131% Activity at 0.3125 uM_tenth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
132% Activity at 0.15625 uM_tenth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
133IC50_Qualifier_6_Range1This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
134IC50_6_Range1IC50 value determined using a sigmoidal dose response equationFloatμM
135Std.Err(IC50)_6_Range1Standard Error of the IC50 valueFloatμM
136nH_6_Range1Hill coefficient determined using sigmoidal dose response equationFloat
137Excluded_Points_eleventh_point_Range1Flags to indicate which of the eleventh dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
138% Activity at 80 uM_eleventh_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
139% Activity at 40 uM_eleventh_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
140% Activity at 20 uM_eleventh_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
141% Activity at 10 uM_eleventh_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
142% Activity at 5 uM_eleventh_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
143% Activity at 2.5 uM_eleventh_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
144% Activity at 1.25 uM_eleventh_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
145% Activity at 0.625 uM_eleventh_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
146% Activity at 0.3125 uM_eleventh_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
147% Activity at 0.15625 uM_eleventh_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
148Excluded_Points_twelfth_point_Range1Flags to indicate which of the twelfth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
149% Activity at 80 uM_twelfth_point_Range1 (80μM**)% inhibition at the test concentrationFloat%
150% Activity at 40 uM_twelfth_point_Range1 (40μM**)% inhibition at the test concentrationFloat%
151% Activity at 20 uM_twelfth_point_Range1 (20μM**)% inhibition at the test concentrationFloat%
152% Activity at 10 uM_twelfth_point_Range1 (10μM**)% inhibition at the test concentrationFloat%
153% Activity at 5 uM_twelfth_point_Range1 (5μM**)% inhibition at the test concentrationFloat%
154% Activity at 2.5 uM_twelfth_point_Range1 (2.5μM**)% inhibition at the test concentrationFloat%
155% Activity at 1.25 uM_twelfth_point_Range1 (1.25μM**)% inhibition at the test concentrationFloat%
156% Activity at 0.625 uM_twelfth_point_Range1 (0.625μM**)% inhibition at the test concentrationFloat%
157% Activity at 0.3125 uM_twelfth_point_Range1 (0.3125μM**)% inhibition at the test concentrationFloat%
158% Activity at 0.15625 uM_twelfth_point_Range1 (0.15625μM**)% inhibition at the test concentrationFloat%
159IC50_Qualifier_1_Range2This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
160IC50_1_Range2IC50 value determined using a sigmoidal dose response equationFloatμM
161Std.Err(IC50)_1_Range2Standard Error of the IC50 valueFloatμM
162nH_1_Range2Hill coefficient determined using sigmoidal dose response equationFloat
163Excluded_Points_first_point_Range2Flags to indicate which of the first dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
164% Activity at 8 uM_first_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
165% Activity at 4 uM_first_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
166% Activity at 2 uM_first_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
167% Activity at 1 uM_first_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
168% Activity at 0.5 uM_first_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
169% Activity at 0.25 uM_first_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
170% Activity at 0.125 uM_first_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
171% Activity at 0.0625 uM_first_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
172% Activity at 0.03125 uM_first_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
173% Activity at 0.015625 uM_first_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
174Excluded_Points_second_point_Range2Flags to indicate which of the second dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
175% Activity at 8 uM_second_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
176% Activity at 4 uM_second_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
177% Activity at 2 uM_second_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
178% Activity at 1 uM_second_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
179% Activity at 0.5 uM_second_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
180% Activity at 0.25 uM_second_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
181% Activity at 0.125 uM_second_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
182% Activity at 0.0625 uM_second_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
183% Activity at 0.03125 uM_second_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
184% Activity at 0.015625 uM_second_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
185IC50_Qualifier_2_Range2This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
186IC50_2_Range2IC50 value determined using a sigmoidal dose response equationFloatμM
187Std.Err(IC50)_2_Range2Standard Error of the IC50 valueFloatμM
188nH_2_Range2Hill coefficient determined using sigmoidal dose response equationFloat
189Excluded_Points_third_point_Range2Flags to indicate which of the third dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
190% Activity at 8 uM_third_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
191% Activity at 4 uM_third_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
192% Activity at 2 uM_third_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
193% Activity at 1 uM_third_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
194% Activity at 0.5 uM_third_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
195% Activity at 0.25 uM_third_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
196% Activity at 0.125 uM_third_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
197% Activity at 0.0625 uM_third_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
198% Activity at 0.03125 uM_third_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
199% Activity at 0.015625 uM_third_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
200Excluded_Points_fourth_point_Range2Flags to indicate which of the fourth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
201% Activity at 8 uM_fourth_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
202% Activity at 4 uM_fourth_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
203% Activity at 2 uM_fourth_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
204% Activity at 1 uM_fourth_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
205% Activity at 0.5 uM_fourth_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
206% Activity at 0.25 uM_fourth_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
207% Activity at 0.125 uM_fourth_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
208% Activity at 0.0625 uM_fourth_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
209% Activity at 0.03125 uM_fourth_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
210% Activity at 0.015625 uM_fourth_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
211IC50_Qualifier_3_Range2This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
212IC50_3_Range2IC50 value determined using a sigmoidal dose response equationFloatμM
213Std.Err(IC50)_3_Range2Standard Error of the IC50 valueFloatμM
214nH_3_Range2Hill coefficient determined using sigmoidal dose response equationFloat
215Excluded_Points_fifth_point_Range2Flags to indicate which of the fifth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
216% Activity at 8 uM_fifth_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
217% Activity at 4 uM_fifth_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
218% Activity at 2 uM_fifth_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
219% Activity at 1 uM_fifth_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
220% Activity at 0.5 uM_fifth_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
221% Activity at 0.25 uM_fifth_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
222% Activity at 0.125 uM_fifth_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
223% Activity at 0.0625 uM_fifth_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
224% Activity at 0.03125 uM_fifth_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
225% Activity at 0.015625 uM_fifth_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
226Excluded_Points_sixth_point_Range2Flags to indicate which of the sixth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
227% Activity at 8 uM_sixth_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
228% Activity at 4 uM_sixth_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
229% Activity at 2 uM_sixth_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
230% Activity at 1 uM_sixth_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
231% Activity at 0.5 uM_sixth_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
232% Activity at 0.25 uM_sixth_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
233% Activity at 0.125 uM_sixth_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
234% Activity at 0.0625 uM_sixth_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
235% Activity at 0.03125 uM_sixth_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
236% Activity at 0.015625 uM_sixth_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
237IC50_Qualifier_4_Range2This qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that valueString
238IC50_4_Range2IC50 value determined using a sigmoidal dose response equationFloatμM
239Std.Err(IC50)_4_Range2Standard Error of the IC50 valueFloatμM
240nH_4_Range2Hill coefficient determined using sigmoidal dose response equationFloat
241Excluded_Points_seventh_point_Range2Flags to indicate which of the seventh dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
242% Activity at 8 uM_seventh_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
243% Activity at 4 uM_seventh_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
244% Activity at 2 uM_seventh_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
245% Activity at 1 uM_seventh_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
246% Activity at 0.5 uM_seventh_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
247% Activity at 0.25 uM_seventh_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
248% Activity at 0.125 uM_seventh_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
249% Activity at 0.0625 uM_seventh_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
250% Activity at 0.03125 uM_seventh_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
251% Activity at 0.015625 uM_seventh_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%
252Excluded_Points_eighth_point_Range2Flags to indicate which of the eighth dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.String
253% Activity at 8 uM_eighth_point_Range2 (8μM**)% inhibition at the test concentrationFloat%
254% Activity at 4 uM_eighth_point_Range2 (4μM**)% inhibition at the test concentrationFloat%
255% Activity at 2 uM_eighth_point_Range2 (2μM**)% inhibition at the test concentrationFloat%
256% Activity at 1 uM_eighth_point_Range2 (1μM**)% inhibition at the test concentrationFloat%
257% Activity at 0.5 uM_eighth_point_Range2 (0.5μM**)% inhibition at the test concentrationFloat%
258% Activity at 0.25 uM_eighth_point_Range2 (0.25μM**)% inhibition at the test concentrationFloat%
259% Activity at 0.125 uM_eighth_point_Range2 (0.125μM**)% inhibition at the test concentrationFloat%
260% Activity at 0.0625 uM_eighth_point_Range2 (0.0625μM**)% inhibition at the test concentrationFloat%
261% Activity at 0.03125 uM_eighth_point_Range2 (0.03125μM**)% inhibition at the test concentrationFloat%
262% Activity at 0.015625 uM_eighth_point_Range2 (0.015625μM**)% inhibition at the test concentrationFloat%

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: 1R21AI082434-01

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