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BioAssay: AID 651598

SAR analysis of small molecule antagonists of the CXCR6 receptor in an APJ-DiscoveRx counter screen panel assay

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(3)
 
 
Active(1)
 
 
Inactive(3)
 
 
 Tested Substances
 Tested Substances
All(6)
 
 
Active(1)
 
 
Inactive(5)
 
 
AID: 651598
Data Source: Burnham Center for Chemical Genomics (SBCCG-A909-CXCR6-DryPowder-Panel-Assay-2)
BioAssay Type: Panel, Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2012-09-26
Hold-until Date: 2013-09-03
Modify Date: 2013-09-04

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compound: 1
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
651601SAR analysis of small molecule antagonists of the CXCR6 receptor in a screening panel assayConfirmatorysame project related to Summary assay
651708SAR analysis of small molecule antagonists of the CXCR6 receptor in a screening panel assay - 3Confirmatorysame 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. Compounds were tested in the primary assay against the CXCR6 receptor. Compounds considered active in this assay were further tested in the same B-arrestin system but against the APJ receptor. This receptor assay was employed to test selectivity of compounds for the CXCR6 chemokine receptor over an unrelated GPCR. Compounds considered active in the APJ assay 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
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescription
ActiveInactive
1IC50_APJ_Mean6apelin 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_3_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
5IC50_4_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
6IC50_5_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
7IC50_6_APJapelin receptor [Homo sapiens] [gi:4885057]
IC50 value determined using a sigmoidal dose response equation
8IC50_CXCR6_Mean15C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
Mean IC50 value of the replicates
9IC50_1_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
10IC50_2_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
11IC50_3_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
12IC50_4_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
13IC50_5_CXCR6C-X-C chemokine receptor type 6 [Homo sapiens] [gi:5730106]
IC50 value determined using a sigmoidal dose response equation
14IC50_6_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 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 79uM to 0.156 uM, 0.8% DMSO). Add 40nl DMSOt 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 2ul/well of Assay media to Col. 1-2 for the positive control.
4) Using the Biotek Dispenser, add 2ul/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: 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
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 < 10 uM the the CXCR6 assay are considered to be active.

Compounds were considered active in the counter screen if

APJ IC50_Mean < 5 * IC50_mean CXCR6 result

Compounds that were found to be active in the CXCR6 assay and not active in the APJ counter screen are considered "active" in this panel. The score is the value from the CXCR6 assay if the compound is active, 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
Show more
TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Outcome_CXCR68C-X-C chemokine receptor type 6 [Homo sapiens]Outcome
2Score_CXCR68Integer
3Outcome_APJ1apelin receptor [Homo sapiens]Outcome
4Score_APJ1Integer
5IC50_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 value1String
6IC50_APJ_MeanIC50 value determined using a sigmoidal dose response equation1FloatμM
7IC50_Qualifier_1_APJThis qualifier is to be used with the next TID, IC50_1. 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
8IC50_1_APJIC50 value determined using a sigmoidal dose response equation2FloatμM
9Std.Err(IC50)_1_APJStandard Error of the IC50 value2FloatμM
10nH_1_APJHill coefficient determined using sigmoidal dose response equation2Float
11Excluded_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
12% Activity at 80 uM_first_point_APJ (80μM**)% Activity at the test concentration2Float%
13% Activity at 40 uM_first_point_APJ (40μM**)% Activity at the test concentration2Float%
14% Activity at 20 uM_first_point_APJ (20μM**)% Activity at the test concentration2Float%
15% Activity at 10 uM_first_point_APJ (10μM**)% Activity at the test concentration2Float%
16% Activity at 5 uM_first_point_APJ (5μM**)% Activity at the test concentration2Float%
17% Activity at 2.5 uM_first_point_APJ (2.5μM**)% Activity at the test concentration2Float%
18% Activity at 1.25 uM_first_point_APJ (1.25μM**)% Activity at the test concentration2Float%
19% Activity at 0.625 uM_first_point_APJ (0.625μM**)% Activity at the test concentration2Float%
20% Activity at 0.3125 uM_first_point_APJ (0.3125μM**)% Activity at the test concentration2Float%
21% Activity at 0.15625 uM_first_point_APJ (0.15625μM**)% Activity at the test concentration2Float%
22IC50_Qualifier_2_APJThis 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 value3apelin receptor [Homo sapiens]String
23IC50_2_APJIC50 value determined using a sigmoidal dose response equation3FloatμM
24Std.Err(IC50)_2_APJStandard Error of the IC50 value3FloatμM
25nH_2_APJHill coefficient determined using sigmoidal dose response equation3Float
26Excluded_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
27% Activity at 80 uM_second_point_APJ (80μM**)% Activity at the test concentration3Float%
28% Activity at 40 uM_second_point_APJ (40μM**)% Activity at the test concentration3Float%
29% Activity at 20 uM_second_point_APJ (20μM**)% Activity at the test concentration3Float%
30% Activity at 10 uM_second_point_APJ (10μM**)% Activity at the test concentration3Float%
31% Activity at 5 uM_second_point_APJ (5μM**)% Activity at the test concentration3Float%
32% Activity at 2.5 uM_second_point_APJ (2.5μM**)% Activity at the test concentration3Float%
33% Activity at 1.25 uM_second_point_APJ (1.25μM**)% Activity at the test concentration3Float%
34% Activity at 0.625 uM_second_point_APJ (0.625μM**)% Activity at the test concentration3Float%
35% Activity at 0.3125 uM_second_point_APJ (0.3125μM**)% Activity at the test concentration3Float%
36% Activity at 0.15625 uM_second_point_APJ (0.15625μM**)% Activity at the test concentration3Float%
37IC50_Qualifier_3_APJThis qualifier is to be used with the next TID, IC50_3. 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 value4apelin receptor [Homo sapiens]String
38IC50_3_APJIC50 value determined using a sigmoidal dose response equation4FloatμM
39Std.Err(IC50)_3_APJStandard Error of the IC50 value4FloatμM
40nH_3_APJHill coefficient determined using sigmoidal dose response equation4Float
41Excluded_Points_third_point_APJFlags 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.4String
42% Activity at 80 uM_third_point_APJ (80μM**)% Activity at the test concentration4Float%
43% Activity at 40 uM_third_point_APJ (40μM**)% Activity at the test concentration4Float%
44% Activity at 20 uM_third_point_APJ (20μM**)% Activity at the test concentration4Float%
45% Activity at 10 uM_third_point_APJ (10μM**)% Activity at the test concentration4Float%
46% Activity at 5 uM_third_point_APJ (5μM**)% Activity at the test concentration4Float%
47% Activity at 2.5 uM_third_point_APJ (2.5μM**)% Activity at the test concentration4Float%
48% Activity at 1.25 uM_third_point_APJ (1.25μM**)% Activity at the test concentration4Float%
49% Activity at 0.625 uM_third_point_APJ (0.625μM**)% Activity at the test concentration4Float%
50% Activity at 0.3125 uM_third_point_APJ (0.3125μM**)% Activity at the test concentration4Float%
51% Activity at 0.15625 uM_third_point_APJ (0.15625μM**)% Activity at the test concentration4Float%
52IC50_Qualifier_4_APJThis qualifier is to be used with the next TID, IC50_4. 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 value5apelin receptor [Homo sapiens]String
53IC50_4_APJIC50 value determined using a sigmoidal dose response equation5FloatμM
54Std.Err(IC50)_4_APJStandard Error of the IC50 value5FloatμM
55nH_4_APJHill coefficient determined using sigmoidal dose response equation5Float
56Excluded_Points_fourth_point_APJFlags 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.5String
57% Activity at 80 uM_fourth_point_APJ (80μM**)% Activity at the test concentration5Float%
58% Activity at 40 uM_fourth_point_APJ (40μM**)% Activity at the test concentration5Float%
59% Activity at 20 uM_fourth_point_APJ (20μM**)% Activity at the test concentration5Float%
60% Activity at 10 uM_fourth_point_APJ (10μM**)% Activity at the test concentration5Float%
61% Activity at 5 uM_fourth_point_APJ (5μM**)% Activity at the test concentration5Float%
62% Activity at 2.5 uM_fourth_point_APJ (2.5μM**)% Activity at the test concentration5Float%
63% Activity at 1.25 uM_fourth_point_APJ (1.25μM**)% Activity at the test concentration5Float%
64% Activity at 0.625 uM_fourth_point_APJ (0.625μM**)% Activity at the test concentration5Float%
65% Activity at 0.3125 uM_fourth_point_APJ (0.3125μM**)% Activity at the test concentration5Float%
66% Activity at 0.15625 uM_fourth_point_APJ (0.15625μM**)% Activity at the test concentration5Float%
67IC50_Qualifier_5_APJThis qualifier is to be used with the next TID, IC50_5. 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 value6apelin receptor [Homo sapiens]String
68IC50_5_APJIC50 value determined using a sigmoidal dose response equation6FloatμM
69Std.Err(IC50)_5_APJStandard Error of the IC50 value6FloatμM
70nH_5_APJHill coefficient determined using sigmoidal dose response equation6Float
71Excluded_Points_fifth_point_APJFlags 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.6String
72% Activity at 80 uM_fifth_point_APJ (80μM**)% Activity at the test concentration6Float%
73% Activity at 40 uM_fifth_point_APJ (40μM**)% Activity at the test concentration6Float%
74% Activity at 20 uM_fifth_point_APJ (20μM**)% Activity at the test concentration6Float%
75% Activity at 10 uM_fifth_point_APJ (10μM**)% Activity at the test concentration6Float%
76% Activity at 5 uM_fifth_point_APJ (5μM**)% Activity at the test concentration6Float%
77% Activity at 2.5 uM_fifth_point_APJ (2.5μM**)% Activity at the test concentration6Float%
78% Activity at 1.25 uM_fifth_point_APJ (1.25μM**)% Activity at the test concentration6Float%
79% Activity at 0.625 uM_fifth_point_APJ (0.625μM**)% Activity at the test concentration6Float%
80% Activity at 0.3125 uM_fifth_point_APJ (0.3125μM**)% Activity at the test concentration6Float%
81% Activity at 0.15625 uM_fifth_point_APJ (0.15625μM**)% Activity at the test concentration6Float%
82IC50_Qualifier_6_APJThis qualifier is to be used with the next TID, IC50_6. 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 value7apelin receptor [Homo sapiens]String
83IC50_6_APJIC50 value determined using a sigmoidal dose response equation7FloatμM
84Std.Err(IC50)_6_APJStandard Error of the IC50 value7FloatμM
85nH_6_APJHill coefficient determined using sigmoidal dose response equation7Float
86Excluded_Points_sixth_point_APJFlags 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.7String
87% Activity at 80 uM_sixth_point_APJ (80μM**)% Activity at the test concentration7Float%
88% Activity at 40 uM_sixth_point_APJ (40μM**)% Activity at the test concentration7Float%
89% Activity at 20 uM_sixth_point_APJ (20μM**)% Activity at the test concentration7Float%
90% Activity at 10 uM_sixth_point_APJ (10μM**)% Activity at the test concentration7Float%
91% Activity at 5 uM_sixth_point_APJ (5μM**)% Activity at the test concentration7Float%
92% Activity at 2.5 uM_sixth_point_APJ (2.5μM**)% Activity at the test concentration7Float%
93% Activity at 1.25 uM_sixth_point_APJ (1.25μM**)% Activity at the test concentration7Float%
94% Activity at 0.625 uM_sixth_point_APJ (0.625μM**)% Activity at the test concentration7Float%
95% Activity at 0.3125 uM_sixth_point_APJ (0.3125μM**)% Activity at the test concentration7Float%
96% Activity at 0.15625 uM_sixth_point_APJ (0.15625μM**)% Activity at the test concentration7Float%
97IC50_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 value8C-X-C chemokine receptor type 6 [Homo sapiens]String
98IC50_CXCR6_Mean*IC50 value determined using a sigmoidal dose response equation8FloatμM
99IC50_Qualifier_1_CXCR6This qualifier is to be used with the next TID, IC50_1. 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
100IC50_1_CXCR6IC50 value determined using a sigmoidal dose response equation9FloatμM
101Std.Err(IC50)_1_CXCR6Standard Error of the IC50 value9FloatμM
102nH_1_CXCR6Hill coefficient determined using sigmoidal dose response equation9Float
103Excluded_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.9String
104% Activity at 80 uM_first_point_CXCR6 (80μM**)% Activity at the test concentration9Float%
105% Activity at 40 uM_first_point_CXCR6 (40μM**)% Activity at the test concentration9Float%
106% Activity at 20 uM_first_point_CXCR6 (20μM**)% Activity at the test concentration9Float%
107% Activity at 10 uM_first_point_CXCR6 (10μM**)% Activity at the test concentration9Float%
108% Activity at 5 uM_first_point_CXCR6 (5μM**)% Activity at the test concentration9Float%
109% Activity at 2.5 uM_first_point_CXCR6 (2.5μM**)% Activity at the test concentration9Float%
110% Activity at 1.25 uM_first_point_CXCR6 (1.25μM**)% Activity at the test concentration9Float%
111% Activity at 0.625 uM_first_point_CXCR6 (0.625μM**)% Activity at the test concentration9Float%
112% Activity at 0.3125 uM_first_point_CXCR6 (0.3125μM**)% Activity at the test concentration9Float%
113% Activity at 0.15625 uM_first_point_CXCR6 (0.15625μM**)% Activity at the test concentration9Float%
114IC50_Qualifier_2_CXCR6This 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 value10C-X-C chemokine receptor type 6 [Homo sapiens]String
115IC50_2_CXCR6IC50 value determined using a sigmoidal dose response equation10FloatμM
116Std.Err(IC50)_2_CXCR6Standard Error of the IC50 value10FloatμM
117nH_2_CXCR6Hill coefficient determined using sigmoidal dose response equation10Float
118Excluded_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.10String
119% Activity at 80 uM_second_point_CXCR6 (80μM**)% Activity at the test concentration10Float%
120% Activity at 40 uM_second_point_CXCR6 (40μM**)% Activity at the test concentration10Float%
121% Activity at 20 uM_second_point_CXCR6 (20μM**)% Activity at the test concentration10Float%
122% Activity at 10 uM_second_point_CXCR6 (10μM**)% Activity at the test concentration10Float%
123% Activity at 5 uM_second_point_CXCR6 (5μM**)% Activity at the test concentration10Float%
124% Activity at 2.5 uM_second_point_CXCR6 (2.5μM**)% Activity at the test concentration10Float%
125% Activity at 1.25 uM_second_point_CXCR6 (1.25μM**)% Activity at the test concentration10Float%
126% Activity at 0.625 uM_second_point_CXCR6 (0.625μM**)% Activity at the test concentration10Float%
127% Activity at 0.3125 uM_second_point_CXCR6 (0.3125μM**)% Activity at the test concentration10Float%
128% Activity at 0.15625 uM_second_point_CXCR6 (0.15625μM**)% Activity at the test concentration10Float%
129IC50_Qualifier_3_CXCR6This qualifier is to be used with the next TID, IC50_3. 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 value11C-X-C chemokine receptor type 6 [Homo sapiens]String
130IC50_3_CXCR6IC50 value determined using a sigmoidal dose response equation11FloatμM
131Std.Err(IC50)_3_CXCR6Standard Error of the IC50 value11FloatμM
132nH_3_CXCR6Hill coefficient determined using sigmoidal dose response equation11Float
133Excluded_Points_third_point_CXCR6Flags 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.11String
134% Activity at 80 uM_third_point_CXCR6 (80μM**)% Activity at the test concentration11Float%
135% Activity at 40 uM_third_point_CXCR6 (40μM**)% Activity at the test concentration11Float%
136% Activity at 20 uM_third_point_CXCR6 (20μM**)% Activity at the test concentration11Float%
137% Activity at 10 uM_third_point_CXCR6 (10μM**)% Activity at the test concentration11Float%
138% Activity at 5 uM_third_point_CXCR6 (5μM**)% Activity at the test concentration11Float%
139% Activity at 2.5 uM_third_point_CXCR6 (2.5μM**)% Activity at the test concentration11Float%
140% Activity at 1.25 uM_third_point_CXCR6 (1.25μM**)% Activity at the test concentration11Float%
141% Activity at 0.625 uM_third_point_CXCR6 (0.625μM**)% Activity at the test concentration11Float%
142% Activity at 0.3125 uM_third_point_CXCR6 (0.3125μM**)% Activity at the test concentration11Float%
143% Activity at 0.15625 uM_third_point_CXCR6 (0.15625μM**)% Activity at the test concentration11Float%
144IC50_Qualifier_4_CXCR6This qualifier is to be used with the next TID, IC50_4. 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 value12C-X-C chemokine receptor type 6 [Homo sapiens]String
145IC50_4_CXCR6IC50 value determined using a sigmoidal dose response equation12FloatμM
146Std.Err(IC50)_4_CXCR6Standard Error of the IC50 value12FloatμM
147nH_4_CXCR6Hill coefficient determined using sigmoidal dose response equation12Float
148Excluded_Points_fourth_point_CXCR6Flags 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.12String
149% Activity at 80 uM_fourth_point_CXCR6 (80μM**)% Activity at the test concentration12Float%
150% Activity at 40 uM_fourth_point_CXCR6 (40μM**)% Activity at the test concentration12Float%
151% Activity at 20 uM_fourth_point_CXCR6 (20μM**)% Activity at the test concentration12Float%
152% Activity at 10 uM_fourth_point_CXCR6 (10μM**)% Activity at the test concentration12Float%
153% Activity at 5 uM_fourth_point_CXCR6 (5μM**)% Activity at the test concentration12Float%
154% Activity at 2.5 uM_fourth_point_CXCR6 (2.5μM**)% Activity at the test concentration12Float%
155% Activity at 1.25 uM_fourth_point_CXCR6 (1.25μM**)% Activity at the test concentration12Float%
156% Activity at 0.625 uM_fourth_point_CXCR6 (0.625μM**)% Activity at the test concentration12Float%
157% Activity at 0.3125 uM_fourth_point_CXCR6 (0.3125μM**)% Activity at the test concentration12Float%
158% Activity at 0.15625 uM_fourth_point_CXCR6 (0.15625μM**)% Activity at the test concentration12Float%
159IC50_Qualifier_5_CXCR6This qualifier is to be used with the next TID, IC50_5. 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 value13C-X-C chemokine receptor type 6 [Homo sapiens]String
160IC50_5_CXCR6IC50 value determined using a sigmoidal dose response equation13FloatμM
161Std.Err(IC50)_5_CXCR6Standard Error of the IC50 value13FloatμM
162nH_5_CXCR6Hill coefficient determined using sigmoidal dose response equation13Float
163Excluded_Points_fifth_point_CXCR6Flags 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.13String
164% Activity at 80 uM_fifth_point_CXCR6 (80μM**)% Activity at the test concentration13Float%
165% Activity at 40 uM_fifth_point_CXCR6 (40μM**)% Activity at the test concentration13Float%
166% Activity at 20 uM_fifth_point_CXCR6 (20μM**)% Activity at the test concentration13Float%
167% Activity at 10 uM_fifth_point_CXCR6 (10μM**)% Activity at the test concentration13Float%
168% Activity at 5 uM_fifth_point_CXCR6 (5μM**)% Activity at the test concentration13Float%
169% Activity at 2.5 uM_fifth_point_CXCR6 (2.5μM**)% Activity at the test concentration13Float%
170% Activity at 1.25 uM_fifth_point_CXCR6 (1.25μM**)% Activity at the test concentration13Float%
171% Activity at 0.625 uM_fifth_point_CXCR6 (0.625μM**)% Activity at the test concentration13Float%
172% Activity at 0.3125 uM_fifth_point_CXCR6 (0.3125μM**)% Activity at the test concentration13Float%
173% Activity at 0.15625 uM_fifth_point_CXCR6 (0.15625μM**)% Activity at the test concentration13Float%
174IC50_Qualifier_6_CXCR6This qualifier is to be used with the next TID, IC50_6. 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 value14C-X-C chemokine receptor type 6 [Homo sapiens]String
175IC50_6_CXCR6IC50 value determined using a sigmoidal dose response equation14FloatμM
176Std.Err(IC50)_6_CXCR6Standard Error of the IC50 value14FloatμM
177nH_6_CXCR6Hill coefficient determined using sigmoidal dose response equation14Float
178Excluded_Points_sixth_point_CXCR6Flags 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.14String
179% Activity at 80 uM_sixth_point_CXCR6 (80μM**)% Activity at the test concentration14Float%
180% Activity at 40 uM_sixth_point_CXCR6 (40μM**)% Activity at the test concentration14Float%
181% Activity at 20 uM_sixth_point_CXCR6 (20μM**)% Activity at the test concentration14Float%
182% Activity at 10 uM_sixth_point_CXCR6 (10μM**)% Activity at the test concentration14Float%
183% Activity at 5 uM_sixth_point_CXCR6 (5μM**)% Activity at the test concentration14Float%
184% Activity at 2.5 uM_sixth_point_CXCR6 (2.5μM**)% Activity at the test concentration14Float%
185% Activity at 1.25 uM_sixth_point_CXCR6 (1.25μM**)% Activity at the test concentration14Float%
186% Activity at 0.625 uM_sixth_point_CXCR6 (0.625μM**)% Activity at the test concentration14Float%
187% Activity at 0.3125 uM_sixth_point_CXCR6 (0.3125μM**)% Activity at the test concentration14Float%
188% Activity at 0.15625 uM_sixth_point_CXCR6 (0.15625μM**)% Activity at the test concentration14Float%

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

Classification
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