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BioAssay: AID 651708

SAR analysis of small molecule antagonists of the CXCR6 receptor in a screening panel assay - 3

Prostate cancer (PCa) is the second leading cause of cancer death in American men and its morbidity has increased globally in recent years. The high mortality rate is closely associated with the spread of malignant cells to various tissues including bone. Nearly 10% of patients whose conditions are diagnosed as PCa initially present with bone metastasis and almost all patients who die of prostate more ..
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 Tested Compounds
 Tested Compounds
All(34)
 
 
Active(6)
 
 
Inactive(28)
 
 
 Tested Substances
 Tested Substances
All(35)
 
 
Active(7)
 
 
Inactive(28)
 
 
AID: 651708
Data Source: Burnham Center for Chemical Genomics (SBCCG-A932-CXCR6-DryPowder-Panel-Assay-3)
BioAssay Type: Panel, Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2012-10-26
Hold-until Date: 2013-09-03
Modify Date: 2013-09-04

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 6
Related Experiments
Show more
AIDNameTypeComment
602244uHTS identification of CXCR6 Inhibitors in a B-arrestin luminescence assayScreeningdepositor-specified cross reference
602249Summary assay for small molecule Inhibitors of CXCR6Summarydepositor-specified cross reference
602409Single concentration confirmation of uHTS hits from a small molecule antagonists of the CXCR6 receptor via a luminescent beta-arrestin assayScreeningsame project related to Summary assay
624129Dose Response confirmation of uHTS hits from a small molecule antagonists of the CXCR6 receptor in a screening assayConfirmatorysame project related to Summary assay
651594Dose Response counterscreen of small molecule antagonists of the CXCR6 receptor using a CXCR5 receptor luminescent beta-arrestin assayConfirmatorysame project related to Summary assay
651598SAR analysis of small molecule antagonists of the CXCR6 receptor in an APJ-DiscoveRx counter screen panel assayConfirmatorysame project related to Summary assay
651601SAR analysis of small molecule antagonists of the CXCR6 receptor in a screening panel assayConfirmatorysame project related to Summary assay
651902SAR analysis of small molecule antagonists of the CXCR6 receptor using a CXCR4 receptor luminescent beta-arrestin counterscreenConfirmatorysame project related to Summary assay
651919SAR analysis of small molecule antagonists of the CXCR6 receptor in a screening panel assay - 4Confirmatorysame project related to Summary assay
651940SAR analysis of small molecule antagonists of the hCXCR6 receptor using a mCXCR6 receptor luminescent beta-arrestin selectivity assayConfirmatorysame project related to Summary assay
651941SAR analysis of small molecule antagonists of the CXCR6 receptor using a CCR6 receptor luminescent beta-arrestin counterscreenConfirmatorysame 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: 1R03MH095589-01 (Cycle 18)
Assay Provider: Gregory Roth Ph.D., Sanford Burnham Medical Research Institute.

Prostate cancer (PCa) is the second leading cause of cancer death in American men and its morbidity has increased globally in recent years. The high mortality rate is closely associated with the spread of malignant cells to various tissues including bone. Nearly 10% of patients whose conditions are diagnosed as PCa initially present with bone metastasis and almost all patients who die of prostate cancers have skeletal involvement. Identifying new mechanisms that control bone metastasis is of great consequence to facilitate the design of therapeutics aimed at decreasing metastatic risk and/or its complications. To address this unmet medical need, our team is actively engaged in exploring the chemical biology, medicinal chemistry, and therapeutic significance of modulating tumor cell trafficking and metastasis via chemokine receptor inhibition. The primary objective of this proposal is to use high throughput screening methods to identify small molecule antagonist probes that selectively inhibit CXCR6. Our team intends to address a key hypothesis: The CXCR6/CXCL16 axis significantly contributes to PCa cell metastasis and subsequent bone invasion. A small molecule antagonist would block cancer cell trafficking; hence mediate a metastatic event and disease progression to bone. Thus, access to pharmacologically available small molecule antagonists will ultimately enable our studies in disease relevant models and allow for a more seamless translational advance to clinical applications.

The project goal is to identify a chemical probe of chemokine CXCR6 receptor function that inhibits the receptor. An antagonist of this receptor would provide a novel research tool to evaluate cancer cell trafficking and bone metastasis in prostrate and other cancers

In this description we utilize enzyme-fragment complementation to directly measure GPCR activation. Unlike imaging or other second messenger assays, the DiscoveRx b-Arrestin assay allows for a direct measure of GPCR activation by detection of b-Arrestin binding to the CXCR6 receptor. In this system, b-Arrestin is fused to an N-terminal deletion mutant of b-gal (termed the enzyme acceptor of EA) and the GPCR of interest is fused to a smaller (42 amino acids), weakly complementing fragment termed ProLink. In cells that stably express these fusion proteins, ligand stimulation results in the interaction of b-Arrestin and the Prolink-tagged GPCR, forcing the complementation of the two b-gal fragments and resulting in the formation of a functional enzyme that converts substrate to detectable signal.

This assay is a follow-up to "uHTS identification of CXCR6 Inhibitors in a B-arrestin luminescence assay", AID 602244, and to study the structure-activity relationship on analogs of the confirmed hits. Compounds are either acquired from commercial sources or synthesized internally. Compounds were tested in the primary assay against the CXCR6 receptor. Compounds were further tested in the same B-arrestin system but against the CCR6 and APJ receptors. Compounds considered active in the CCR6 and APJ assays are non-selective, non-specific and/or assay artifacts of the primary assay and are not desired.

REFERENCES
Hu, W; Zhen, X; Xiong, B; Wang, B; Zhang, W; Zhou, W CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cells. Cancer Sci 2008, 99, 1362-1369.

Matloubian, M; David, A; Engel, S; Ryan, JE; Cyster, JG A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nature Immunol 2000, 1, 298-304.

Chandrasekar B, Bysani S, Mummidi S. CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation. J Biol Chem 2004, 279, 3188-3196.
Panel Information
CXCR6-APJ-CCR6
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescription
ActiveInactive
1IC50_APJ_Mean134apelin receptor [Homo sapiens] [gi:4885057]
Mean IC50 value of the replicates
2IC50_1_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
3IC50_2_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
4IC50_CCR6_Mean35C-C chemokine receptor type 6 [Homo sapiens] [gi:37187860]
Mean IC50 value of the replicates
5IC50_1_CCR6C-C chemokine receptor type 6 [Homo sapiens] [gi:37187860]
IC50 value determined using a sigmoidal dose response equation
6IC50_2_CCR6C-C chemokine receptor type 6 [Homo sapiens] [gi:37187860]
IC50 value determined using a sigmoidal dose response equation
7IC50_CXCR6_Mean728C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
Mean IC50 of the replicates
8IC50_1_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
9IC50_2_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation

§ Panel component ID.
Protocol
1)
A. Brief Description of the APJ assay:
The purpose of this assay is to detect antagonists that inhibit the activation of the Angiotensin II receptor-like 1 (Apelin receptor) in the CHO-K1 AGTRL-1 beta-Arrestin Cell Line in 1536-well plate format in uHTS mode.
B. Materials:
Angiotensin II receptor-like 1 (AGTRL-1) Cell Line (DiscoveRx, Cat# 93-0250C2)
F12 nutrient mix HAMs (Invitrogen, Cat# 11765)
Fetal Bovine Serum, heat-inactivated (Hyclone, Cat# SH30396)
100X Penicillin/Streptomycin Solution (Invitrogen, Cat#15140-122)
Hygromycin B (Roche, Cat# 10843555001)
Geneticin (MPBiomedicals, Cat # 1672548)
Trypsin-EDTA 0.25% (Invitrogen, Cat# 25200-056)
Cell Dissociation Buffer (Invitrogen, Cat# 13151)
DPBS (Hyclone, Cat# 30028.02)
T225 TC Flask (Nunc, Cat# 159934)
Cell strainer, 40 um (BD, Cat# 352340)
1536-well, white, solid-bottom, Kalypsys compatible, TC plate (Corning)
Apelin-13 (Sigma-Aldrich, Cat# A6469)
PathHunter Detection Reagents (DiscoveRx, Cat# 93-0001)
Galacton Star
Emerald 11
Cell Assay Buffer
C. uHTS Procedures:
Day1 Cell Seeding
1) Plate 1000 cells/well in 4 uL of assay media into columns 1-48 of a 1536-well assay plate, using straight tip dispense on a Kalypsys dispenser.
2) Centrifuge plates at 500 rpm for 1 minute on a Vspin centrifuge. Use Kalypsys metal lids.
3) Incubate overnight at 37 degrees, 100% relative humidity, 5% CO2 for 16-18 hours.
Day2 Compound Addition
1) Centrifuge compound plates at 500 rpm for 1 minute on a Vspin centrifuge.
2) Using LabCyte Echo, transfer 60 nL from a 2 mM Echo qualified plate containing test compounds into assay plate Col. 5 - 48 (final concentration of test compounds is 20 uM, 1% DMSO). Transfer 60 nL of DMSO to positive and negative control wells in Columns 1 - 4.
3) Immediately following compound/DMSO transfer via the Echo, using the Kalypsys Dispenser, transfer 2ul/well of Assay media to Col. 1-2 for the positive control wells.
4) Using the Kalypsys Dispenser, add 2ul/well of 30 nM Apelin-13 (FAC = 10 nM) in assay media to Col. 3-48 for the negative control and test compound wells .
5) Centrifuge plates at 500 rpm for 1 minute on a Vspin centrifuge.
6) Incubate plates at 25 degrees in the dark for 90 minutes.
7) Following 90 minute incubation, deliver 3.0 uL of Detection Reagent solution to each assay plate (Columns 1 - 48) using a Kalypsys dispenser.
8) Centrifuge plates at 2000 rpm for 3 minute on a Vspin centrifuge.
9) Incubate plates for 60 minutes at 25 degrees in the dark.
10) Read plates using the Viewlux using a luminescence protocol.
D. Recipes:
Growth Media
F12 nutrient mix HAMs supplemented with 10% hi-FBS, 1X Penicillin/Streptomycin; selection reagents: 300ug/ml Hygromycin B, 800ug/ml Geneticin
Assay Media
Same as Growth Media without the selection reagents
Trypsin
Dilute 0.25% Trypsin/EDTA to 0.05% Trypsin/EDTA using DPBS
Positive Control
Growth Media with 30 nM Apelin-13
Detection Reagent
Use the following ratio to prepare the detection reagent:
Galacton Star : Emerald II : Assay Buffer = 1 : 5 : 19
2)
A. Brief Description of the CCR6 Assay:
The purpose of this assay is to detect antagonists that inhibit the activation of the CCR6 receptor in the CHO-K1 beta-Arrestin Cell Line in 1536-well plate format in uHTS mode.
B. Materials:
PathHunter CHO-K1 CCR6 b-arrestin cell line (DiscoveRx, Cat# 93-0194C2)
F12 nutrient mix HAMs (Invitrogen, Cat# 11765)
Fetal Bovine Serum, heat-inactivated (Hyclone, Cat# SH30396)
100X Penicillin/Streptomycin Solution (Invitrogen, Cat#15140-122)
Hygromycin B (Roche, Cat# 10843555001)
Geneticin (MPBiomedicals, Cat # 1672548)
Trypsin-EDTA 0.25% (Invitrogen, Cat# 25200-056)
Cell Dissociation Buffer (Invitrogen, Cat# 13151)
DPBS (Hyclone, Cat# 30028.02)
T225 TC Flask (Nunc, Cat# 159934)
1536-well, white, solid-bottom, Kalypsys compatible, TC plate (Aurora)
MIP-3a/CCL20 peptide (R&D Systems, Cat# 360MP)
PathHunter Detection Reagents (DiscoveRx, Cat# 93-0001)
Galacton Star
Emerald 11
Cell Assay Buffer
C. uHTS Procedures:
Day1 Cell Seeding
1) Plate 800 cells/well in 4 uL of assay media into columns 1-48 of a 1536-well assay plate, using Biotek dispenser.
2) Centrifuge plates at 500 rpm for 1 minute on a Vspin centrifuge. Use Kalypsys metal lids.
3) Incubate overnight at 37 oC, 100% relative humidity, 5% CO2 for 16-18 hours.
Day2 Compound Addition
1) Centrifuge compound plates at 500 rpm for 1 minute on a Vspin centrifuge.
2) Using LabCyte Echo 555, transfer 40 nL of DMSO to positive and negative control wells in columns 1 - 4 and 45-48, respectively. Using a dose response protocol, transfer compounds from 10 mM and 0.312 mM Echo qualified plates into assay plate columns 5 - 45. (Final concentrations range 66 uM to 0.128 uM, 10 doses, with 0.66% DMSO.)
3) Immediately following compound/DMSO transfer via the Echo, using the Biotek Dispenser, transfer 2 ul/well of Assay media to Col. 1-2 for the positive control wells.
4) Using the Biotek Dispenser, add 2 ul/well of 42 nM MIP3a/CCL20 (FAC = 14 nM) in assay media to Col. 3-48 for the negative control and test compound wells.
5) Centrifuge plates at 500 rpm for 1 minute on a Vspin centrifuge.
6) Incubate plates at 25 degrees in the dark for 90 minutes.
7) Following 90 minute incubation, deliver 3.0 uL of Detection Reagent solution to each assay plate (Columns 1 - 48) using a Biotek dispenser.
8) Centrifuge plates at 2000 rpm for 2 minute on a Vspin centrifuge.
9) Incubate plates for 60 minutes at 25 degrees in the dark.
10) Read plates using the Envision using a luminescence protocol.
D. Recipes:
Growth Media
F12 nutrient mix HAMs supplemented with 10% hi-FBS, 1X Penicillin/Streptomycin; selection reagents: 300ug/ml Hygromycin B, 800ug/ml Geneticin
Assay Media/Positive Control
Same as Growth Media without the selection reagents and only 2.5% hi-FBS
Trypsin
Dilute 0.25% Trypsin/EDTA to 0.05% Trypsin/EDTA using DPBS
Negative Control
Growth Media with 14 nM MIP3a/CCL20
Detection Reagent
Use the following ratio to prepare the detection reagent:
Galacton Star : Emerald II : Assay Buffer = 1 : 5 : 19
3)
A. Brief Description of the CXCR6 Assay:
The purpose of this assay is to detect antagonists that cause the inhibit the Chemokine CXCR6 receptor in the CHO-K1 PathHunter CHO-K1 CXCR6 b-arrestin cell line in 1536-well plate format.
B. Materials:
PathHunter CHO-K1 CXCR6 b-arrestin cell line (DiscoveRx, Cat# 93-0205C2)
F12 nutrient mix HAMs (Invitrogen, Cat# 11765)
Fetal Bovine Serum, heat-inactivated (Hyclone, Cat# SH30396)
100X Penicillin/Streptomycin Solution (Invitrogen, Cat#15140-122)
Hygromycin B (Roche, Cat# 10843555001)
Geneticin (MPBiomedicals, Cat# 1672548)
Trypsin-EDTA 0.25% (Invitrogen, Cat# 25200-056)
Cell Dissociation Buffer (Invitrogen, Cat# 13151)
DPBS (Hyclone, Cat# 30028.02)
T225 TC Flask (Nunc, Cat# 159934)
Cell strainer, 40 um (BD, Cat# 352340)
1536-well, white, solid-bottom, Kalypsys compatible, TC plate (Corning)
CXCCL16 (R&D Systems, Cat# 976-CX)
PathHunter Detection Reagents (DiscoveRx, Cat# 93-0001)
Galacton Star
Emerald 11
Cell Assay Buffer
C. uHTS Procedures:
Day1 Cell Seeding
1) Plate 800 cells/well in 3 uL of assay media into columns 1-48 of a 1536-well assay plate, using combi dispenser.
2) Centrifuge plates at 500 rpm for 1 minute on a Vspin centrifuge.
3) Put Kalypsis lids on and incubate overnight at 37 degrees, 100% relative humidity, 5% CO2 for 16-18 hours.
Day2 Compound Addition
1) Centrifuge compound plates at 500 rpm for 1 minute on a Vspin centrifuge.
2) Using LabCyte Echo, transfer 40-2.5 nl from a 10 mM and 0.312 mM Echo qualified plate containing DPI liquid reordered test into assay plate Col. 5 - 44 (final concentration of test compounds is 79 uM to 0.156 uM, 0.8% DMSO). Add 40 nl DMSO to positive and negative control wells in Columns 1 - 4 and 45-48.
3) Immediately following compound/DMSO transfer via the Echo, using the Biotek Dispenser, transfer 2 ul/well of Assay media to Col. 1-2 for the positive control.
4) Using the Biotek Dispenser, add 2 ul/well of 25 nM CXCL16 (FAC = 10 nM) in assay media to Col. 3-48 for the negative control and test compounds.
5) Centrifuge plates at 1000 rpm for 1 minute on a Vspin centrifuge.
6) Incubate plates at 25 degrees in the dark for 90 minutes.
7) Following 90 minute incubation, deliver 3.0 uL of Detection Reagent solution to each assay plate (Columns 1 - 48) using a Biotek dispenser.
8) Centrifuge plates at 2000 rpm for 3 minute on a Vspin centrifuge.
9) Incubate plates for 60 minutes at 25 degrees in the dark.
10) Read plates using the Envision plate reader using a luminescence protocol.
D. Recipes:
Growth Media
F12 nutrient mix HAMs supplemented with 10% hi-FBS, 1X Penicillin/Streptomycin; selection reagents: 300 ug/ml Hygromycin B, 800 ug/ml Geneticin
Assay Media
Same as Growth Media without the selection reagents
Trypsin
Dilute 0.25% Trypsin/EDTA to 0.05% Trypsin/EDTA using DPBS
Negative Control
Growth Media with 10 nM CXCL16
Detection Reagent
Use the following ratio to prepare the detection reagent:
Galacton Star : Emerald II : Assay Buffer = 1 : 5 : 19
Comment
Compounds that with an IC50_Mean > 30 uM in APJ and CCR6 assays and IC50_Mean <= 10 in the CXCR6 assay are considered to be active.
Compounds that were found to be active in both assays are considered "active" in this panel and the score is the average of the values from the two panels, otherwise the panel score is 81.
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.
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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TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Outcome_CXCR67C-X-C chemokine receptor type 6 [Homo sapiens]Outcome
2Score_CXCR67Integer
3Outcome_CCR64C-C chemokine receptor type 6 [Homo sapiens]Outcome
4Score_CCR64Integer
5Outcome_APJ1apelin receptor [Homo sapiens]Outcome
6SCORE_APJ1Integer
7IC50_CCR6_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 value4C-C chemokine receptor type 6 [Homo sapiens]String
8IC50_CCR6_Mean*IC50 value determined using a sigmoidal dose response equation4FloatμM
9IC50_Qualifier_1_CCR6This 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 value5C-C chemokine receptor type 6 [Homo sapiens]String
10IC50_1_CCR6*IC50 value determined using a sigmoidal dose response equation5FloatμM
11Std.Err(IC50)_1_CCR6Standard Error of the IC50 value5FloatμM
12nH_1_CCR6Hill coefficient determined using sigmoidal dose response equation5Float
13Excluded_Points_first_point_CCR6Flags 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.5String
14% Activity at 79 uM_first_point_CCR6 (79μM**)% Activity at the test concentration5Float%
15% Activity at 39.5 uM_first_point_CCR6 (39.5μM**)% Activity at the test concentration5Float%
16% Activity at 19.75 uM_first_point_CCR6 (19.75μM**)% Activity at the test concentration5Float%
17% Activity at 9.875 uM_first_point_CCR6 (9.875μM**)% Activity at the test concentration5Float%
18% Activity at 4.9375 uM_first_point_CCR6 (4.9375μM**)% Activity at the test concentration5Float%
19% Activity at 2.46875 uM_first_point_CCR6 (2.46875μM**)% Activity at the test concentration5Float%
20% Activity at 1.234375 uM_first_point_CCR6 (1.23438μM**)% Activity at the test concentration5Float%
21% Activity at 0.6171875 uM_first_point_CCR6 (0.617188μM**)% Activity at the test concentration5Float%
22% Activity at 0.3085938 uM_first_point_CCR6 (0.308594μM**)% Activity at the test concentration5Float%
23% Activity at 0.1542969 uM_first_point_CCR6 (0.154297μM**)% Activity at the test concentration5Float%
24IC50_Qualifier_2_CCR6This qualifier is to be used with the next TID, IC50_2. 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 value6C-C chemokine receptor type 6 [Homo sapiens]String
25IC50_2_CCR6*IC50 value determined using a sigmoidal dose response equation6FloatμM
26Std.Err(IC50)_2_CCR6Standard Error of the IC50 value6FloatμM
27nH_2_CCR6Hill coefficient determined using sigmoidal dose response equation6Float
28Excluded_Points_second_point_CCR6Flags 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.6String
29% Activity at 79 uM_second_point_CCR6 (79μM**)% Activity at the test concentration6Float%
30% Activity at 39.5 uM_second_point_CCR6 (39.5μM**)% Activity at the test concentration6Float%
31% Activity at 19.75 uM_second_point_CCR6 (19.75μM**)% Activity at the test concentration6Float%
32% Activity at 9.875 uM_second_point_CCR6 (9.875μM**)% Activity at the test concentration6Float%
33% Activity at 4.9375 uM_second_point_CCR6 (4.9375μM**)% Activity at the test concentration6Float%
34% Activity at 2.46875 uM_second_point_CCR6 (2.46875μM**)% Activity at the test concentration6Float%
35% Activity at 1.234375 uM_second_point_CCR6 (1.23438μM**)% Activity at the test concentration6Float%
36% Activity at 0.6171875 uM_second_point_CCR6 (0.617188μM**)% Activity at the test concentration6Float%
37% Activity at 0.3085938 uM_second_point_CCR6 (0.308594μM**)% Activity at the test concentration6Float%
38% Activity at 0.1542969 uM_second_point_CCR6 (0.154297μM**)% Activity at the test concentration6Float%
39IC50_APJ_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 value1apelin receptor [Homo sapiens]String
40IC50_APJ_Mean*IC50 value determined using a sigmoidal dose response equation1FloatμM
41IC50_Qualifier_1_APJThis 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 value2apelin receptor [Homo sapiens]String
42IC50_1_APJ*IC50 value determined using a sigmoidal dose response equation2FloatμM
43Std.Err(IC50)_1_APJStandard Error of the IC50 value2FloatμM
44nH_1_APJHill coefficient determined using sigmoidal dose response equation2Float
45Excluded_Points_first_point_APJFlags 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.2String
46% Activity at 79 uM_first_point_APJ (79μM**)% Activity at the test concentration2Float%
47% Activity at 39.5 uM_first_point_APJ (39.5μM**)% Activity at the test concentration2Float%
48% Activity at 19.75 uM_first_point_APJ (19.75μM**)% Activity at the test concentration2Float%
49% Activity at 9.875 uM_first_point_APJ (9.875μM**)% Activity at the test concentration2Float%
50% Activity at 4.9375 uM_first_point_APJ (4.9375μM**)% Activity at the test concentration2Float%
51% Activity at 2.46875 uM_first_point_APJ (2.46875μM**)% Activity at the test concentration2Float%
52% Activity at 1.234375 uM_first_point_APJ (1.23438μM**)% Activity at the test concentration2Float%
53% Activity at 0.6171875 uM_first_point_APJ (0.617188μM**)% Activity at the test concentration2Float%
54% Activity at 0.3085938 uM_first_point_APJ (0.308594μM**)% Activity at the test concentration2Float%
55% Activity at 0.1542969 uM_first_point_APJ (0.154297μM**)% Activity at the test concentration2Float%
56IC50_Qualifier_2_APJThis 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 value3apelin receptor [Homo sapiens]String
57IC50_2_APJ*IC50 value determined using a sigmoidal dose response equation3FloatμM
58Std.Err(IC50)_2_APJStandard Error of the IC50 value3FloatμM
59nH_2_APJHill coefficient determined using sigmoidal dose response equation3Float
60Excluded_Points_second_point_APJFlags 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.3String
61% Activity at 79 uM_second_point_APJ (79μM**)% Activity at the test concentration3Float%
62% Activity at 39.5 uM_second_point_APJ (39.5μM**)% Activity at the test concentration3Float%
63% Activity at 19.75 uM_second_point_APJ (19.75μM**)% Activity at the test concentration3Float%
64% Activity at 9.875 uM_second_point_APJ (9.875μM**)% Activity at the test concentration3Float%
65% Activity at 4.9375 uM_second_point_APJ (4.9375μM**)% Activity at the test concentration3Float%
66% Activity at 2.46875 uM_second_point_APJ (2.46875μM**)% Activity at the test concentration3Float%
67% Activity at 1.234375 uM_second_point_APJ (1.23438μM**)% Activity at the test concentration3Float%
68% Activity at 0.6171875 uM_second_point_APJ (0.617188μM**)% Activity at the test concentration3Float%
69% Activity at 0.3085938 uM_second_point_APJ (0.308594μM**)% Activity at the test concentration3Float%
70% Activity at 0.1542969 uM_second_point_APJ (0.154297μM**)% Activity at the test concentration3Float%
71IC50_CXCR6_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 value7C-X-C chemokine receptor type 6 [Homo sapiens]String
72IC50_CXCR6_Mean*IC50 value determined using a sigmoidal dose response equation7FloatμM
73IC50_Qualifier_1_CXCR6This 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 value8C-X-C chemokine receptor type 6 [Homo sapiens]String
74IC50_1_CXCR6*IC50 value determined using a sigmoidal dose response equation8FloatμM
75Std.Err(IC50)_1_CXCR6Standard Error of the IC50 value8FloatμM
76nH_1_CXCR6Hill coefficient determined using sigmoidal dose response equation8Float
77Excluded_Points_first_point_CXCR6Flags 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.8String
78% Activity at 79 uM_first_point_CXCR6 (79μM**)% Activity at the test concentration8Float%
79% Activity at 39.5 uM_first_point_CXCR6 (39.5μM**)% Activity at the test concentration8Float%
80% Activity at 19.75 uM_first_point_CXCR6 (19.75μM**)% Activity at the test concentration8Float%
81% Activity at 9.875 uM_first_point_CXCR6 (9.875μM**)% Activity at the test concentration8Float%
82% Activity at 4.9375 uM_first_point_CXCR6 (4.9375μM**)% Activity at the test concentration8Float%
83% Activity at 2.46875 uM_first_point_CXCR6 (2.46875μM**)% Activity at the test concentration8Float%
84% Activity at 1.234375 uM_first_point_CXCR6 (1.23438μM**)% Activity at the test concentration8Float%
85% Activity at 0.6171875 uM_first_point_CXCR6 (0.617188μM**)% Activity at the test concentration8Float%
86% Activity at 0.3085938 uM_first_point_CXCR6 (0.308594μM**)% Activity at the test concentration8Float%
87% Activity at 0.1542969 uM_first_point_CXCR6 (0.154297μM**)% Activity at the test concentration8Float%
88IC50_Qualifier_2_CXCR6This 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 value9C-X-C chemokine receptor type 6 [Homo sapiens]String
89IC50_2_CXCR6IC50 value determined using a sigmoidal dose response equation9FloatμM
90Std.Err(IC50)_2_CXCR6Standard Error of the IC50 value9FloatμM
91nH_2_CXCR6Hill coefficient determined using sigmoidal dose response equation9Float
92Excluded_Points_second_point_CXCR6Flags 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.9String
93% Activity at 79 uM_second_point_CXCR6 (79μM**)% Activity at the test concentration9Float%
94% Activity at 39.5 uM_second_point_CXCR6 (39.5μM**)% Activity at the test concentration9Float%
95% Activity at 19.75 uM_second_point_CXCR6 (19.75μM**)% Activity at the test concentration9Float%
96% Activity at 9.875 uM_second_point_CXCR6 (9.875μM**)% Activity at the test concentration9Float%
97% Activity at 4.9375 uM_second_point_CXCR6 (4.9375μM**)% Activity at the test concentration9Float%
98% Activity at 2.46875 uM_second_point_CXCR6 (2.46875μM**)% Activity at the test concentration9Float%
99% Activity at 1.234375 uM_second_point_CXCR6 (1.23438μM**)% Activity at the test concentration9Float%
100% Activity at 0.6171875 uM_second_point_CXCR6 (0.617188μM**)% Activity at the test concentration9Float%
101% Activity at 0.3085938 uM_second_point_CXCR6 (0.308594μM**)% Activity at the test concentration9Float%
102% Activity at 0.1542969 uM_second_point_CXCR6 (0.154297μM**)% Activity at the test concentration9Float%

* Activity Concentration. ** Test Concentration. § Panel component ID.
Additional Information
Grant Number: 1R03MH095589-01 (Cycle 18)

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