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BioAssay: AID 2117

Late stage results from the probe development effort to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR).

Name: Late stage results from the probe development effort to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR). ..more
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 Tested Compounds
 Tested Compounds
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Active(7)
 
 
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 Tested Substances
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Active(7)
 
 
AID: 2117
Data Source: The Scripps Research Institute Molecular Screening Center (ROR_MOD_PROBES_LATE_STAGE)
BioAssay Type: Panel, Primary, Primary Screening, Single Concentration Activity Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-11-09
Hold-until Date: 2010-05-04
Modify Date: 2010-02-23

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 7
Related Experiments
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AIDNameTypeProbeComment
2139Summary of probe development efforts to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR).Summary2 depositor-specified cross reference: Summary AID (EBNA1 inhibitors).
2277Center Based Initiative to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR): luminescence-based high throughput cell-based assay to identify modulators of human nuclear receptors.Screening depositor-specified cross reference: Screening assay (Nuclear receptor profiling in singlicate).
561Primary Cell-based High Throughput Screening assay for inhibitors of the Retinoic Acid Receptor-related orphan receptor A (RORA)Screening same project related to Summary assay
610Dose-response cell-based assay for inhibitors of the Retinoic Acid Receptor-related orphan receptor A (RORA)Confirmatory same project related to Summary assay
1901Summary of probe development efforts to identify inhibitors of the Retinoic Acid Receptor-related orphan receptor A (RORA).Summary same project related to Summary assay
463078Late stage assay provider results from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescent-based assay to identify RORA inhibitorsOther same project related to Summary assay
463143Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based assay to identify activators of the liver X receptor (LXR)Screening same project related to Summary assay
463144Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based assay to identify inhibitors of glucose-6-phosphatase (G6PC)Other same project related to Summary assay
463145Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based assay to identify activators of the farnesoid X receptor (FXR)Screening same project related to Summary assay
463147Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based assay to identify RORG inhibitorsScreening same project related to Summary assay
463148Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based assay to identify inhibitors of the human herpes virus VP16 transcriptional activator protein (VP16)Screening same project related to Summary assay
463150Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based dose response assay to identify activators of the liver X receptor (LXR)Confirmatory same project related to Summary assay
463151Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescent-based dose response assay to identify RORG inhibitorsConfirmatory same project related to Summary assay
463152Late stage assay provider results from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based dose response assay to identify RORA inhibitorsConfirmatory same project related to Summary assay
463172Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): luminescence-based cell-based dose response assay to identify inhibitors of glucose-6-phosphatase (G6PC)Confirmatory same project related to Summary assay
504899Late stage assay provider results from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): Diet-Induced obesity (DIO) mouse model studies to assess the effect of probe candidate on hepatic glucose productionOther same project related to Summary assay
504906Late stage assay provider results from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): radioligand binding assay for RORa using [3H]25-hydroxycholesterol to determine whether probe candidates bind directly to RORaOther same project related to Summary assay
504907Late stage assay provider results from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptors (RORA): fluorescence-based real-time polymerase chain reaction assay to determine the effect of probe candidates on endogenous expression of glucose-6-phosphatase (G6PC)Other same project related to Summary assay
624276Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptor Gamma (RORC): radioligand binding for ROR gamma using Scintillation Proximity Assay (SPA)Confirmatory1 same project related to Summary assay
624277Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptor Gamma (RORC): Luminescence-based cell-based assays using RORE-Luc, IL-17-Luc, and ABCA1-Luc ReportersOther1 same project related to Summary assay
624278Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptor Gamma (RORC): Fluorescence-based cell-based QPCR assays to determine endogenous expression of ROR gamma target genes, proinflammatory IL-17 and IL-23ROther1 same project related to Summary assay
624279Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptor Gamma (RORC): luminescence-based cell-based dose response panel assay against ROR alpha, ROR gamma, LXR, FXR, and VP16Confirmatory1 same project related to Summary assay
Description:
Source (MLPCN Center Name): The Scripps Research Institute Molecular Screening Center (SRISMC)
Center Affiliation: The Scripps Research Institute, TSRI
Assay Provider: Patrick Griffin, TSRI
Network: Molecular Library Probe Production Center Network (MLPCN)
Grant Proposal Number: U54 MH084512
Grant Proposal PI: Patrick Griffin, TSRI
External Assay ID: ROR_MOD_PROBES_LATE_STAGE

Name: Late stage results from the probe development effort to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR).

Description:

Nuclear receptors are a family of small molecule and hormone-regulated transcription factors that share conserved DNA-binding and ligand-binding domains. Small pharmacological compounds able to bind to the cleft of the ligand-binding domain could alter its conformation and subsequently modify transcription of target genes. Such ligand agonists and/or antagonists have already been successfully designed for 23 nuclear receptors among the 48 previously identified in the human genome (1-3). RORalpha (RORa; RORA; NR1F1) is one of three related orphan nuclear receptors, including RORbeta (ROR#; RORB; NR1F2) and RORgamma (ROR?; RORC; NR1F3), known as "Retinoic Acid Receptor-related orphan receptors" (4).

RORA has unusual potential as a therapeutic target for the "metabolic syndrome" which results in pathologies such as insulin resistance, dyslipidemia, hypertension, and a pro-inflammatory state, that greatly elevates the risk of diabetes and atherosclerosis (5).The related RORC demonstrates significant expression in metabolic tissues such as liver, adipose, and skeletal muscle (6). These two receptors are implicated in several key aspects of this metabolic pathogenesis. For instance, the staggerer mouse, which carries a homozygous germline inactivation of RORA, shows low body weight, high food consumption (7-9), elevated angiogenesis in response to ischemia (10), susceptibility to atherosclerosis (9), and an abnormal serum lipid profile (11). RORG null mice exhibit normal plasma cholesterol levels, but when bred with the RORA staggerer mice, the resulting RORalpha/gamma knockout exhibits hypoglycemia not found in the single mutant animals. These studies reveal the functional redundancy of RORa and RORg in regulating blood glucose levels and highlight the need for RORalpha/gamma ligands that can bind to these receptors and modulate their transcriptional activity.

Summary of Probe Development Effort:

This AID reports the results of the Center-based effort to identify modulator probes of RORa and RORg. Following primary screening of a cell-based GAL4-human nuclear receptor profiling assay (Assay 1), certain compounds were identified as possible candidates for probe development. Compounds derived from these initial candidates were purchased as powders or synthesized at the SRIMSC and were tested for their ability to inhibit RORa and RORg in luciferase-based reporter assays performed in dose response assays starting at a nominal concentration of 20 micromolar (Assays 1 and 2). Compounds were subsequently counterscreened in dose response assays against the liver X receptor (LXR) and the farnesoid X receptor (FXR) to determine selectivity (Assays 3 and 4). Finally, compounds of interest were tested at a single concentration of 10 micromolar against VP16 to determine whether they were non-selective or cytotoxic (Assay 5), and probe candidates were tested against glucose-6-phosphatase to determine biologic efficacy on an ROR target gene.

The above probe development efforts resulted in the identification of two probes. The benzenesulfonamide compound SID 85257301 previously identified as a selective agonist of LXR (12) was identified here as a novel RORa/g inverse agonist probe that decreases the transcriptional activity of both ROR receptors (IC50 values = 2.0 and 1.73 micromolar, respectively). The second probe, SID 85257298 synthesized at the SRIMSC, was found to decrease RORa transcriptional activity (IC50 value = 2.47 micromolar). SID 85257298 represents an improvement over the prior art due to its lack of activity for LXR. Probe compound SID85257298 does not have activity against RORg (IC50 > 20 micromolar). These two probes are useful tools for examining ROR biology.

The results of our probe development efforts can be found at http://molscreen.florida.scripps.edu/probes.shtml. A manuscript has been published (13).

References:

(1) Evans RM. The nuclear receptor superfamily: a rosetta stone for physiology. Mol Endocrinol 19:1429-1438, 2005.
(2) Kliewer SA, Lehmann JM, and Willson TM. Orphan nuclear receptors: shifting endocrinology into reverse. Science 284: 757-760, 1999.
(3) Li Y, Lambert MH, and Xu HE. Activation of nuclear receptors: a perspective from structural genomics. Structure (Camb) 11: 741-746., 2003.
(4) Jetten AM, Kurebayashi S, and Ueda E. The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes. Prog Nucleic Acid Res Mol Biol 69: 205-247, 2001.
(5) Grundy SM, Brewer HB, Jr., Cleeman JI, Smith SC, Jr., and Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 24: e13-18, 2004.
(6) Medvedev A, Yan ZH, Hirose T, Gigu#re V, Jetten AM. Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element. Gene. 1996 Nov 28;181(1-2):199-206.
(7) Bertin R, Guastavino JM, and Portet R. Effects of cold acclimation on the energetic metabolism of the staggerer mutant mouse. Physiol Behav 47: 377-380, 1990.
(8) Guastavino JM, Bertin R, and Portet R. Effects of the rearing temperature on the temporal feeding pattern of the staggerer mutant mouse. Physiol Behav 49: 405-409, 1991.
(9) Mamontova A, Seguret-Mace S, Esposito B, Chaniale C, Bouly M, Delhaye-Bouchaud N, Luc G, Staels B, Duverger N, Mariani J, and Tedgui A. Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha. Circulation 98: 2738-2743., 1998.
(10) Besnard S, Silvestre J-S, Duriez M, Bakouche J, Lemaigre-Dubreuil Y, Mariani J, Levy BI, and Tedgui A. Increased ischemia-induced angiogenesis in the staggerer mouse, a mutant of the nuclear receptor RORa. Circ Res 89: 1209-1215, 2001.
(11) Raspe E, Duez H, Gervois P, Fievet C, Fruchart J-C, Besnard S, Mariani J, Tedgui A, and Staels B. Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha. J Biol Chem 276: 2865-2871, 2001.
(12) Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B. Role of LXRs in control of lipogenesis. Genes Dev. 2000 Nov 15;14(22):2831-8.
(13) The benzenesulfoamide T0901317 is a novel RORa/? Inverse Agonist. Kumar N, Solt LA, Conkright JJ, Wang Y, Istrate MA, Busby SA, Garcia-Ordonez R, Burris TP, Griffin PR. Mol Pharmacol. 2010 Feb;77(2):228-36.

Keywords:

Late stage, probes, RAR-related orphan receptor A, ROR alpha, RORa, RORA, nuclear receptor, library, counterscreen, low throughput assay, RZRA, ROR1, ROR2, ROR3, NR1F1, inhibitor, activator, transcriptional assay, assay provider, center based initiative, center-based, luciferase, luminescence, ROR gamma, RORg, RORC, RORG, LXR, FXR, NR1F3, Primary screen, Scripps Florida, The Scripps Research Institute Molecular Screening Center, SRIMSC, Molecular Libraries Probe Production Centers Network, MLPCN.
Panel Information
Assays
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescriptionAdditional Information
ActiveInactive
1RORA51retinoid-related orphan receptor alpha [Homo sapiens] [gi:216409696]
Taxonomy id: 9606
Gene id: 6095
2RORG42retinoid-related orphan receptor gamma [Homo sapiens] [gi:216409700]
Taxonomy id: 9606
Gene id: 6097
3LXR33nuclear receptor subfamily 1, group H, member 2 [Homo sapiens] [gi:85362735]
Taxonomy id: 9606
Gene id: 7376
4FXR15nuclear receptor subfamily 1, group H, member 4 [Homo sapiens] [gi:4826980]
Taxonomy id: 9606
Gene id: 9971
5VP1616transactivating tegument protein VP16 [Human herpesvirus 1] [gi:9629429]
Taxonomy id: 10298
Gene id: 2703416
6G6Pase Promoter2glucose-6-phosphatase, catalytic subunit [Homo sapiens] [gi:4557599]
Taxonomy id: 9606
Gene id: 2538

§ Panel component ID.
Protocol
Please see AID 2277, the probe development assays below , reference(13), and Summary AID 2139 for all protocols performed in this Center-based probe development effort.
RORA Inhibition Assay (Assay 1):
The purpose of these assays is to identify compounds that inhibit RORa activity. This assay employs the RORa-expressing cell line from a GAL4 nuclear receptor library. In this assay, HEK293T cells co-transfected with a GAL4DBD-RORaLBD construct (GAL4-RORa) and a GAL4UAS-luciferase reporter construct are incubated for 18-24 hours with test compounds. The presence in this cell line of required co-activators allows the expression of luciferase driven by activated RORa nuclear receptors. As designed, compounds that inhibit RORa activity will prevent activation of the GAL4-RORa construct, thereby preventing GAL4DBD-mediated activation of the GAL4UAS-luciferase reporter, leading to a decrease in well luminescence. Compounds were tested in a 10-point dilution series starting at a nominal concentration of 20 micromolar. Six replicates were performed for each assay.
RORG Inhibition Assay (Assay 2):
The purpose of these assays is to identify compounds that inhibit RORg activity. This assay employs the RORg-expressing cell line from a GAL4 nuclear receptor library. In this assay, HEK293T cells co-transfected with a GAL4DBD-RORgLBD construct (GAL4-RORg) and a GAL4UAS-luciferase reporter construct are incubated for 18-24 hours with test compounds. The presence in this cell line of required co-activators allows the expression of luciferase driven by activated RORg nuclear receptors. As designed, compounds that inhibit RORg activity will prevent activation of the GAL4-RORg construct, thereby preventing GAL4DBD-mediated activation of the GAL4UAS-luciferase reporter, leading to a decrease in well luminescence. Compounds were tested in a 10-point dilution series starting at a nominal concentration of 20 micromolar. Six replicates were performed for each assay.
LXR Activation Assay (Assay 3):
The purpose of these assays is to identify compounds that increase liver X receptor (LXR) activity. This assay employs the LXR-expressing cell line from a GAL4 nuclear receptor library. In this assay, HEK293T cells co-transfected with a GAL4DBD-LXRLBD construct (GAL4-LXR) and a GAL4UAS-luciferase reporter construct are incubated for 18-24 hours with test compounds. The presence in this cell line of required co-activators allows the expression of luciferase driven by activated LXR nuclear receptors. As designed, compounds that activate LXR activity will activate the GAL4-LXR construct, thereby increasing GAL4DBD-mediated activation of the GAL4UAS-luciferase reporter, leading to an increase in well luminescence. Compounds were tested in a 10-point dilution series starting at a nominal concentration of 20 micromolar. Six replicates were performed for each assay.
FXR Activation Assay (Assay 4):
The purpose of this assay is to identify compounds that increase farnesoid X receptor (FXR) activity. This assay employs the FXR-expressing cell line from a GAL4 nuclear receptor library. In this assay, HEK293T cells co-transfected with a GAL4DBD-FXRLBD construct (GAL4-FXR) and a GAL4UAS-luciferase reporter construct are incubated for 18-24 hours with test compounds. The presence in this cell line of required co-activators allows the expression of luciferase driven by activated FXR nuclear receptors. As designed, compounds that activate FXR activity will activate the GAL4-FXR construct, thereby increasing GAL4DBD-mediated activation of the GAL4UAS-luciferase reporter, leading to an increase in well luminescence. Compounds were tested in a 10-point dilution series starting at a nominal concentration of 20 micromolar. Six replicates were performed for each assay.
VP16 Inhibition Counterscreen Assay (Assay 5):
In this counterscreen assay the nuclear receptor plasmid was replaced by the GAL4DBD-VP16LBD plasmid, which expresses the strong transactivation domain of the herpes simplex virus Virion Protein 16 (VP16) fused to the GAL4 DBD. Cells are co-transfected with the 5xGAL4 response element (UAS) luciferase reporter to monitor GAL4DBD-VP16LBD activity, followed by incubation with test compounds for 18-24 hours. As designed, compounds that inhibit VP16 activity will decrease pGAL4DBD-VP16LBD activity, leading to reduced activation of the pG5-luc and decreased well luminescence. These compounds are likely to be nonselective inhibitors or cytotoxic. Compounds were tested in singlicate at a final nominal concentration of 10 micromolar. Six replicates were performed for each assay.
Glucose-6-Phosphatase (G6Pase) Promoter Assay (Assay 6):
The purpose of this assay is to determine whether probe candidates can modulate ROR target genes in cells. In these assays 293T cells were co-transfected with pS6 control plasmid or pS6 containing full length RORa along with G6Pase promoter. SRC-2 as a coactivator was also co-transfected with G6Pase promoter. Dose-response curve was determined by treating the transfected cells with varying concentrations of compound for 20 hours. Luciferase activity was measured and relative change was determined by normalizing to cells treated with vehicle only. Each data point was performed in eight replicates, n=8. Compounds were tested in a 10-point dilution series starting at a nominal concentration of 20 micromolar.
Comment
Probes were identified.
Result Definitions
Show more
TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1RORA (Qualifier) Activity Qualifier identifies if the resultant data IC50 came from a fitted curve or was determined manually to be less than or greater than its listed IC50 concentration.1retinoid-related orphan receptor alpha [Homo sapiens]String
2RORA (IC50) *The concentration at which 50 percent of the inhibition in the inhibitor assay is observed; (IC50) shown in molar.1FloatμM
3RORA (Inhibition at 0.6 nM) (0.0006μM**)Value of % inhibition at 0.6 nanomolar inhibitor concentration; average of six measurements.1Float%
4RORA (Inhibition at 2.0 nM) (0.002μM**)Value of % inhibition at 2.0 nanomolar inhibitor concentration; average of six measurements.1Float%
5RORA (Inhibition at 6.0 nM) (0.006μM**)Value of % inhibition at 6.0 nanomolar inhibitor concentration; average of six measurements.1Float%
6RORA (Inhibition at 20.0 nM) (0.02μM**)Value of % inhibition at 20.0 nanomolar inhibitor concentration; average of six measurements.1Float%
7RORA (Inhibition at 60.0 nM) (0.06μM**)Value of % inhibition at 60.0 nanomolar inhibitor concentration; average of six measurements.1Float%
8RORA (Inhibition at 200.0 nM) (0.2μM**)Value of % inhibition at 200.0 nanomolar inhibitor concentration; average of six measurements.1Float%
9RORA (Inhibition at 600.0 nM) (0.6μM**)Value of % inhibition at 600.0 nanomolar inhibitor concentration; average of six measurements.1Float%
10RORA (Inhibition at 2.0 uM) (2μM**)Value of % inhibition at 2.0 micromolar inhibitor concentration; average of six measurements.1Float%
11RORA (Inhibition at 6.0 uM) (6μM**)Value of % inhibition at 6.0 micromolar inhibitor concentration; average of six measurements.1Float%
12RORA (Inhibition at 20.0 uM) (20μM**)Value of % inhibition at 20.0 micromolar inhibitor concentration; average of six measurements.1Float%
13RORA (Outcome)The panel assay outcome. One of Active or Inactive.1Outcome
14RORG (Qualifier) Activity Qualifier identifies if the resultant data IC50 came from a fitted curve or was determined manually to be less than or greater than its listed IC50 concentration.2retinoid-related orphan receptor gamma [Homo sapiens]String
15RORG (IC50) *The concentration at which 50 percent of the inhibition in the inhibitor assay is observed; (IC50) shown in molar.2FloatμM
16RORG (Inhibition at 0.6 nM) (0.0006μM**)Value of % inhibition at 0.6 nanomolar inhibitor concentration; average of six measurements.2Float%
17RORG (Inhibition at 2.0 nM) (0.002μM**)Value of % inhibition at 2.0 nanomolar inhibitor concentration; average of six measurements.2Float%
18RORG (Inhibition at 6.0 nM) (0.006μM**)Value of % inhibition at 6.0 nanomolar inhibitor concentration; average of six measurements.2Float%
19RORG (Inhibition at 20.0 nM) (0.02μM**)Value of % inhibition at 20.0 nanomolar inhibitor concentration; average of six measurements.2Float%
20RORG (Inhibition at 60.0 nM) (0.06μM**)Value of % inhibition at 60.0 nanomolar inhibitor concentration; average of six measurements.2Float%
21RORG (Inhibition at 200.0 nM) (0.2μM**)Value of % inhibition at 200.0 nanomolar inhibitor concentration; average of six measurements.2Float%
22RORG (Inhibition at 600.0 nM) (0.6μM**)Value of % inhibition at 600.0 nanomolar inhibitor concentration; average of six measurements.2Float%
23RORG (Inhibition at 2.0 uM) (2μM**)Value of % inhibition at 2.0 micromolar inhibitor concentration; average of six measurements.2Float%
24RORG (Inhibition at 6.0 uM) (6μM**)Value of % inhibition at 6.0 micromolar inhibitor concentration; average of six measurements.2Float%
25RORG (Inhibition at 20.0 uM) (20μM**)Value of % inhibition at 20.0 micromolar inhibitor concentration; average of six measurements.2Float%
26RORG (Outcome)The panel assay outcome. One of Active or Inactive.2Outcome
27LXR (Qualifier) Activity Qualifier identifies if the resultant data EC50 came from a fitted curve or was determined manually to be less than or greater than its listed EC50 concentration.3nuclear receptor subfamily 1, group H, member 2 [Homo sapiens]String
28LXR (EC50)*The concentration at which 50 percent of the activation in the activator assay is observed; (EC50) shown in molar.3FloatμM
29LXR (Activation at 0.6 nM) (0.0006μM**)Value of % activation at 0.6 nanomolar activator concentration; average of six measurements.3Float%
30LXR (Activation at 2.0 nM) (0.002μM**)Value of % activation at 2.0 nanomolar activator concentration; average of six measurements.3Float%
31LXR (Activation at 6.0 nM) (0.006μM**)Value of % activation at 6.0 nanomolar activator concentration; average of six measurements.3Float%
32LXR (Activation at 20.0 nM) (0.02μM**)Value of % activation at 20.0 nanomolar activator concentration; average of six measurements.3Float%
33LXR (Activation at 60.0 nM) (0.06μM**)Value of % activation at 60.0 nanomolar activator concentration; average of six measurements.3Float%
34LXR (Activation at 200.0 nM) (0.2μM**)Value of % activation at 200.0 nanomolar activator concentration; average of six measurements.3Float%
35LXR (Activation at 600.0 nM) (0.6μM**)Value of % activation at 600.0 nanomolar activator concentration; average of six measurements.3Float%
36LXR (Activation at 2.0 uM) (2μM**)Value of % activation at 2.0 micromolar activator concentration; average of six measurements.3Float%
37LXR (Activation at 6.0 uM) (6μM**)Value of % activation at 6.0 micromolar activator concentration; average of six measurements.3Float%
38LXR (Activation at 20.0 uM) (20μM**)Value of % activation at 20.0 micromolar activator concentration; average of six measurements.3Float%
39LXR (Outcome)The panel assay outcome. One of Active or Inactive.3Outcome
40FXR (Qualifier) Activity Qualifier identifies if the resultant data EC50 came from a fitted curve or was determined manually to be less than or greater than its listed EC50 concentration.4nuclear receptor subfamily 1, group H, member 4 [Homo sapiens]String
41FXR (EC50) *The concentration at which 50 percent of the activation in the activator assay is observed; (EC50) shown in molar.4FloatμM
42FXR (Activation at 0.6 nM) (0.0006μM**)Value of % activation at 0.6 nanomolar activator concentration; average of six measurements.4Float%
43FXR (Activation at 2.0 nM) (0.002μM**)Value of % activation at 2.0 nanomolar activator concentration; average of six measurements.4Float%
44FXR (Activation at 6.0 nM) (0.006μM**)Value of % activation at 6.0 nanomolar activator concentration; average of six measurements.4Float%
45FXR (Activation at 20.0 nM) (0.02μM**)Value of % activation at 20.0 nanomolar activator concentration; average of six measurements.4Float%
46FXR (Activation at 60.0 nM) (0.06μM**)Value of % activation at 60.0 nanomolar activator concentration; average of six measurements.4Float%
47FXR (Activation at 200.0 nM) (0.2μM**)Value of % activation at 200.0 nanomolar activator concentration; average of six measurements.4Float%
48FXR (Activation at 600.0 nM) (0.6μM**)Value of % activation at 600.0 nanomolar activator concentration; average of six measurements.4Float%
49FXR (Activation at 2.0 uM) (2μM**)Value of % activation at 2.0 micromolar activator concentration; average of six measurements.4Float%
50FXR (Activation at 6.0 uM) (6μM**)Value of % activation at 6.0 micromolar activator concentration; average of six measurements.4Float%
51FXR (Activation at 20.0 uM) (20μM**)Value of % activation at 20.0 micromolar activator concentration; average of six measurements.4Float%
52FXR (Outcome)The panel assay outcome. One of Active or Inactive.4Outcome
53VP16 (Inhibition) (10μM**)Indicates normalized percent inhibition at a nominal compound concentration of 10 micromolar. Average of six replicates.5transactivating tegument protein VP16 [Human herpesvirus 1]Float%
54VP16 (Max Fold Change) (10μM**)Indicates normalized fold change at a nominal compound concentration of 10 micromolar. Average of six replicates5Float%
55VP16 (Standard Deviation, Max Fold Change) (10μM**)Indicates the standard deviation of the normalized fold change at a nominal compound concentration of 10 micromolar. 5Float
56VP16 (Outcome)The panel assay outcome. One of Active or Inactive.5Outcome
57G6Pase Promoter (Qualifier) Activity Qualifier identifies if the resultant data IC50 came from a fitted curve or was determined manually to be less than or greater than its listed IC50 concentration.6glucose-6-phosphatase, catalytic subunit [Homo sapiens]String
58G6Pase Promoter (IC50) The concentration at which 50 percent of the inhibition in the inhibitor assay is observed; (IC50) shown in molar.6FloatμM
59G6Pase Promoter (Inhibition at 0.6 nM) (0.0006μM**)Value of % inhibition at 0.6 nanomolar inhibitor concentration; average of eight measurements.6Float%
60G6Pase Promoter (Inhibition at 2.0 nM) (0.002μM**)Value of % inhibition at 2.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
61G6Pase Promoter (Inhibition at 6.0 nM) (0.006μM**)Value of % inhibition at 6.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
62G6Pase Promoter (Inhibition at 20.0 nM) (0.02μM**)Value of % inhibition at 20.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
63G6Pase Promoter (Inhibition at 60.0 nM) (0.06μM**)Value of % inhibition at 60.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
64G6Pase Promoter (Inhibition at 200.0 nM) (0.2μM**)Value of % inhibition at 200.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
65G6Pase Promoter (Inhibition at 600.0 nM) (0.6μM**)Value of % inhibition at 600.0 nanomolar inhibitor concentration; average of eight measurements.6Float%
66G6Pase Promoter (Inhibition at 2.0 uM) (2μM**)Value of % inhibition at 2.0 micromolar inhibitor concentration; average of eight measurements.6Float%
67G6Pase Promoter (Inhibition at 6.0 uM) (6μM**)Value of % inhibition at 6.0 micromolar inhibitor concentration; average of eight measurements.6Float%
68G6Pase Promoter (Inhibition at 20.0 uM) (20μM**)Value of % inhibition at 20.0 micromolar inhibitor concentration; average of eight measurements.6Float%
69G6Pase Promoter (Outcome)The panel assay outcome. One of Active or Inactive.6Outcome

* Activity Concentration. ** Test Concentration. § Panel component ID.
Additional Information
Grant Number: U54 MH084512

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