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BioAssay: AID 652011

SAR Analysis small molecule inhibitors of HIF-1a in a panel assay

Most solid tumors and their metastases experience regions of hypoxia, which promotes both tumor progression and resistance to therapy. Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1a and HIF-2a. HIF-1a and HIF-2a are non-redundant and regulate both overlapping and unique downstream target genes. HIF-1a has been associated with poor patient survival in multiple more ..
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 Tested Compounds
 Tested Compounds
All(61)
 
 
Active(9)
 
 
Inactive(52)
 
 
 Tested Substances
 Tested Substances
All(67)
 
 
Active(10)
 
 
Inactive(57)
 
 
AID: 652011
Data Source: Burnham Center for Chemical Genomics (SBCCG-A958-HIF-1a-DryPowder_Panel-Assay)
BioAssay Type: Panel, Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2013-02-02
Hold-until Date: 2014-02-01
Modify Date: 2014-02-05

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: 9
Related Experiments
AIDNameTypeComment
624352uHTS identification of HIF-2a Inhibitors in a luminesence assayScreeningdepositor-specified cross reference
624357Summary assay for small molecule inhibitors of HIF-2aSummarydepositor-specified cross reference
651580Single concentration confirmation of uHTS identification of HIF-2a Inhibitors in a luminesence assayScreeningsame project related to Summary assay
651581Dose response confirmation of uHTS identification of HIF-2a Inhibitors in screening - selectivity counterscreen assaysConfirmatorysame project related to Summary assay
651589Single concentration confirmation of HIF-2a Inhibitors in a HIF-1a counterscreen in human MiAPaCa-2 Cells luciferase reporter assayScreeningsame project related to Summary assay
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, La Jolla, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R03 DA033980-01A1
Assay Provider: Mei Yee Koh, Ph.D., University of Texas M.D. Anderson Cancer Center

Most solid tumors and their metastases experience regions of hypoxia, which promotes both tumor progression and resistance to therapy. Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1a and HIF-2a. HIF-1a and HIF-2a are non-redundant and regulate both overlapping and unique downstream target genes. HIF-1a has been associated with poor patient survival in multiple tumor types and is currently being pursued as a target for inhibition for cancer therapy(1,2). HIF-2a has also been associated with poor patient prognosis in specific tumor types such as renal cell carcinoma (RCC), neuroblastoma, glioblastoma (GBM) and non-small cell lung cancer (NSCLC)(3-6). The tumor type specific function of HIF-2a has been linked with the ability of HIF-2a (but not HIF-1a) to co-operate with a number of oncoproteins such as c-Myc, EGFR and K-Ras(5,7,8) and also to activate genes involved in proliferation, invasion and in the maintenance of cancer stem cells (CSCs)(9,10). Hence, although the validity of HIF-1a as a target in multiple tumor types cannot be denied, emerging data suggest that in certain settings, the specific inhibition of HIF-2a versus HIF-1a would be warranted. Additionally, the newly established role of HIF-2a in the maintenance of neoplastic but not in normal stem cells, suggests that HIF-2a inhibition may provide a novel strategy for the targeting of CSCs 11, 12, 13. Thus our hypothesis is that the specific inhibition of HIF-2a will be a useful strategy for treating HIF-2a driven tumors and for targeting the CSC population. The overall goal of the study is to identify small molecule specific inhibitors of HIF-2a that will lead to the development of new anti-cancer therapies.

The goal of this assay is to confirm hits in "uHTS identification of HIF-2a Inhibitors in a luminesence assay", AID 624352. Compounds that are active in the Hif-2a and HIF-2a_PANC assays, but inactive in the HIF-1a counter screen are selective in the panel. Compounds are either acquired from commercial sources or synthesized internally.


REFERENCES
1. Gordan J D, Bertout J A, Hu C J, Diehl J A,Simon M C. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 2007; 11: 335-47.
2. Scrideli C A, Carlotti C G, Jr., Mata J F, Neder L, Machado H R, Oba-Sinjo S M et al. Prognostic significance of co-overexpression of the EGFR/IGFBP-2/HIF-2A genes in astrocytomas. J Neurooncol 2007; 83: 233-9.
3. Kim W Y, Perera S, Zhou B, Carretero J, Yeh J J, Heathcote S A et al. HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest 2009; 119: 2160-70.
4. Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 2006; 10: 413-23.
5. Franovic A, Holterman C E, Payette J,Lee S. Human cancers converge at the HIF-2alpha oncogenic axis. Proc Natl Acad Sci U S A 2009; 106: 21306-11.
6. Giatromanolaki A, Koukourakis M I, Sivridis E, Turley H, Talks K, Pezzella F et al. Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer 2001; 85: 881-90.
7. Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009; 15: 501-13.
8. Seidel S, Garvalov B K, Wirta V, von Stechow L, Schanzer A, Meletis K et al. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain 2010; 133: 983-95.
9. Pietras A, Hansford L M, Johnsson A S, Bridges E, Sjolund J, Gisselsson D et al. HIF-2alpha maintains an undifferentiated state in neural crest-like human neuroblastoma tumor-initiating cells. Proc Natl Acad Sci U S A 2009; 106: 16805-10.
10. Qing G,Simon M C. Hypoxia inducible factor-2alpha: a critical mediator of aggressive tumor phenotypes. Curr Opin Genet Dev 2009; 19: 60-6.
11. Carroll V A,Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006; 66: 6264-70.
12. Dutta D, Ray S, Vivian J L,Paul S. Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem 2008; 283: 25404-13.
13. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16: 678-86.
Panel Information
HIF-2a panel
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescription
ActiveInactive
1IC50_Mean_HIF2a1651endothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50_Mean value determined using a sigmoidal dose response equation for the replicates
2IC50_1_HIF2aendothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50 value determined using a sigmoidal dose response equation
3IC50_2_HIF2aendothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50 value determined using a sigmoidal dose response equation
4IC50_Mean_Qualifier_HIF2a (PANC cells)2740endothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50_Mean value determined using a sigmoidal dose response equation for the replicates
5IC50_1_HIF2a_PANCendothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50 value determined using a sigmoidal dose response equation
6IC50_2_HIF2a_PANCendothelial PAS domain-containing protein 1 [Homo sapiens] [gi:40254439]
IC50 value determined using a sigmoidal dose response equation
7IC50_Mean_HIF1a607hypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens] [gi:4504385]
IC50_Mean value determined using a sigmoidal dose response equation for the replicates
8IC50_1_HIF1ahypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens] [gi:4504385]
IC50 value determined using a sigmoidal dose response equation
9IC50_2_HIF1ahypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens] [gi:4504385]
IC50 value determined using a sigmoidal dose response equation

§ Panel component ID.
Protocol
HIF-1a
Assay Materials:
MIAPaCa-2 pancreatic cells (Assay Provider)
DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)
Fetal Bovine Serum (Hyclone SH30396.03)
Penicillin Streptomycin solution (Invitrogen 15140122)
L-glutamine (100X ) (Invitrogen 25030081)
G418 (50 mg/mL) (Omega Scientific GN-04)
TrypLE (Invitrogen 12563)
Desferoxiamine (Sigma D9533-1G)
One-Glo (Promega E6120)
I. Cell Addition
1- Dispense 3 uL/well of cells at 2.5x10^5 cells/ml to col 1-48.
2- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.
3 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.
II. Reagent Addition
4-Dispense 1 ul/well 200 uM desferoxiamine in assay media to columns 5-48
III. Compound Addition:
5- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5nl of 10 mM stock and 40-2.5 nl of 0.3125mM stock. All wells are backfilled to 40 nl DMSO (1% DMSO)
6- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.
7 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.
IV. Reagent Addition
8- Dispense 3 uL/well of One-Glo using Combi dispenser to all columns.
9- Spin down plates without lids on Vspin at 2000 rpm for 1 min
10- Incubate plates at room temperature for 10 mins
V. Reading plates:
11-Read on luminescence protocol on Envision
HIF-2a Assay
Assay Materials:
786-0 renal cell carcinoma cells (Assay Provider)
DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)
Fetal Bovine Serum (Hyclone SH30396.03)
Penicillin Streptomycin solution (Invitrogen 15140122)
L-glutamine (100X ) (Invitrogen 25030081)
G418 (50 mg/mL) (Omega Scientific GN-04)
TrypLE (Invitrogen 12563)
Steady-Glo (E2550)
I. Compound Addition:
1- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5 nl from 10 mM stock and 40-2.5 nl from 0.3125 mM stock. All wells are backfilled to 40 nl DMSO (1% DMSO)
II. Reagent Addition
2- Dispense 4 uL/well of assay media to col 1-4.
3- Dispense 4 uL/well of cells at 2.5x10^5 cells/ml to col 5-48.
4- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.
5 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.
6- Dispense 3 uL/well of Steady-Glo using Biotek dispenser to all columns.
7- Spin down plates without lids on Vspin at 2000 rpm for 1 min
8- Incubate plates at room temperature for 10 mins
III. Reading plates:
9-Read on luminescence protocol on Viewlux
HIF-2a PANC
Assay Materials:
PANC pancreatic cells (Assay Provider)
DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)
Fetal Bovine Serum (Hyclone SH30396.03)
Penicillin Streptomycin solution (Invitrogen 15140122)
L-glutamine (100X ) (Invitrogen 25030081)
G418 (50 mg/mL) (Omega Scientific GN-04)
TrypLE (Invitrogen 12563)
Desferoxiamine (Sigma D9533-1G)
One-Glo (Promega E6120)
I. Cell Addition
1- Dispense 3 uL/well of cells at 2.5x10^5 cells/ml to col 1-48.
2- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.
3 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.
II. Reagent Addition
4-Dispense 1 ul/well 200 uM desferoxiamine in assay media to columns 5-48
III. Compound Addition:
5- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5 nl of 10 mM stock and 40-2.5 nl of 0.3125 mM stock. All wells are backfilled to 40nl DMSO (1% DMSO)
6- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.
7 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.
IV. Reagent Addition
8- Dispense 3 uL/well of One-Glo using Combi dispenser to all columns.
9- Spin down plates without lids on Vspin at 2000 rpm for 1 min
10- Incubate plates at room temperature for 10 mins
V. Reading plates:
11-Read on luminescence protocol on Envision
Comment
Compounds that are active in the IC50_HIF-2a and IC50_HIF-2a_PANC assays and inactive in the IC50_HIF-1a assay are specific inhibitors of the reaction.
Compounds that have an IC50_HIF-2a_Mean <= 10 uM are inhibitors of the reaction.
Compounds that have IC50_HIF-2a_Mean_PANC < = 10 are inhibitors of the reaction
Compounds that have IC50_HIF-1a_Mean <= 10 are non-specific inhibitors of the reaction and marked as inactive and given a score of 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.
Categorized Comment - additional comments and annotations
From PubChem:
Assay Cell Type: MIA PaCa-2
Result Definitions
Show more
TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1PUBCHEM_ACTIVITY_SCORE_HIF2a1endothelial PAS domain-containing protein 1 [Homo sapiens]Integer
2PubChem_Activity_Outcome_HIF2a1Outcome
3PUBCHEM_ACTIVITY_SCORE_HIF2a_PANC4endothelial PAS domain-containing protein 1 [Homo sapiens]Integer
4PubChem_Activity_Outcome_HIF2a_Panc4Outcome
5PUBCHEM_ACTIVITY_SCORE_HIF1a7hypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]Integer
6PubChem_Activity_Outcome_HIF1a7Outcome
7IC50_Mean_Qualifier_HIF2aThis 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 value1endothelial PAS domain-containing protein 1 [Homo sapiens]String
8IC50_Mean_HIF2aIC50 value determined using a sigmoidal dose response equation1FloatμM
9IC50_Mean_Qualifier_HIF2a (PANC cells)This 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 value4endothelial PAS domain-containing protein 1 [Homo sapiens]String
10IC50_Mean_HIF2a (PANC cells)*IC50 value determined using a sigmoidal dose response equation4FloatμM
11IC50_Mean_Qualifier_HIF1aThis 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 value7hypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]String
12IC50_Mean_HIF1aIC50 value determined using a sigmoidal dose response equation7FloatμM
13IC50_Qualifier_1_HIF2aThis 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 value2endothelial PAS domain-containing protein 1 [Homo sapiens]String
14IC50_1_HIF2aIC50 value determined using a sigmoidal dose response equation2FloatμM
15Std.Err(IC50)_1_HIF2aStandard Error of the IC50 value2FloatμM
16nH_1_HIF2aHill coefficient determined using sigmoidal dose response equation2Float
17Excluded_Points_first_point_HIF2aFlags 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
18% Activity at 99 uM_first_point_HIF2a (99μM**)% Activity at the test concentration2Float%
19% Activity at 49.5 uM_first_point_HIF2a (49.5μM**)% Activity at the test concentration2Float%
20% Activity at 24.75 uM_first_point_HIF2a (24.75μM**)% Activity at the test concentration2Float%
21% Activity at 12.375 uM_first_point_HIF2a (12.375μM**)% Activity at the test concentration2Float%
22% Activity at 6.1875 uM_first_point_HIF2a (6.1875μM**)% Activity at the test concentration2Float%
23% Activity at 3.09375 uM_first_point_HIF2a (3.09375μM**)% Activity at the test concentration2Float%
24% Activity at 1.546875 uM_first_point_HIF2a (1.54688μM**)% Activity at the test concentration2Float%
25% Activity at 0.7734375 uM_first_point_HIF2a (0.773438μM**)% Activity at the test concentration2Float%
26% Activity at 0.3867188 uM_first_point_HIF2a (0.386719μM**)% Activity at the test concentration2Float%
27% Activity at 0.1933594 uM_first_point_HIF2a (0.193359μM**)% Activity at the test concentration2Float%
28IC50_Qualifier_2_HIF2aThis 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 value3endothelial PAS domain-containing protein 1 [Homo sapiens]String
29IC50_2_HIF2aIC50 value determined using a sigmoidal dose response equation3FloatμM
30Std.Err(IC50)_2_HIF2aStandard Error of the IC50 value3FloatμM
31nH_2_HIF2aHill coefficient determined using sigmoidal dose response equation3Float
32Excluded_Points_second_point_HIF2aFlags 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
33% Activity at 99 uM_second_point_HIF2a (99μM**)% Activity at the test concentration3Float%
34% Activity at 49.5 uM_second_point_HIF2a (49.5μM**)% Activity at the test concentration3Float%
35% Activity at 24.75 uM_second_point_HIF2a (24.75μM**)% Activity at the test concentration3Float%
36% Activity at 12.375 uM_second_point_HIF2a (12.375μM**)% Activity at the test concentration3Float%
37% Activity at 6.1875 uM_second_point_HIF2a (6.1875μM**)% Activity at the test concentration3Float%
38% Activity at 3.09375 uM_second_point_HIF2a (3.09375μM**)% Activity at the test concentration3Float%
39% Activity at 1.546875 uM_second_point_HIF2a (1.54688μM**)% Activity at the test concentration3Float%
40% Activity at 0.7734375 uM_second_point_HIF2a (0.773438μM**)% Activity at the test concentration3Float%
41% Activity at 0.3867188 uM_second_point_HIF2a (0.386719μM**)% Activity at the test concentration3Float%
42% Activity at 0.1933594 uM_second_point_HIF2a (0.193359μM**)% Activity at the test concentration3Float%
43IC50_Qualifier_1_HIF2a_PANCThis 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 value5endothelial PAS domain-containing protein 1 [Homo sapiens]String
44IC50_1_HIF2a_PANCIC50 value determined using a sigmoidal dose response equation5FloatμM
45Std.Err(IC50)_1_HIF2a_PANCStandard Error of the IC50 value5FloatμM
46nH_1_HIF2a_PANCHill coefficient determined using sigmoidal dose response equation5Float
47Excluded_Points_first_point_HIF2a_PANCFlags 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
48% Activity at 99 uM_first_point_HIF2a_PANC (99μM**)% Activity at the test concentration5Float%
49% Activity at 49.5 uM_first_point_HIF2a_PANC (49.5μM**)% Activity at the test concentration5Float%
50% Activity at 24.75 uM_first_point_HIF2a_PANC (24.75μM**)% Activity at the test concentration5Float%
51% Activity at 12.375 uM_first_point_HIF2a_PANC (12.375μM**)% Activity at the test concentration5Float%
52% Activity at 6.1875 uM_first_point_HIF2a_PANC (6.1875μM**)% Activity at the test concentration5Float%
53% Activity at 3.09375 uM_first_point_HIF2a_PANC (3.09375μM**)% Activity at the test concentration5Float%
54% Activity at 1.546875 uM_first_point_HIF2a_PANC (1.54688μM**)% Activity at the test concentration5Float%
55% Activity at 0.7734375 uM_first_point_HIF2a_PANC (0.773438μM**)% Activity at the test concentration5Float%
56% Activity at 0.3867188 uM_first_point_HIF2a_PANC (0.386719μM**)% Activity at the test concentration5Float%
57% Activity at 0.1933594 uM_first_point_HIF2a_PANC (0.193359μM**)% Activity at the test concentration5Float%
58IC50_Qualifier_2_HIF2a_PANCThis 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 value6endothelial PAS domain-containing protein 1 [Homo sapiens]String
59IC50_2_HIF2a_PANCIC50 value determined using a sigmoidal dose response equation6FloatμM
60Std.Err(IC50)_2_HIF2a_PANCStandard Error of the IC50 value6FloatμM
61nH_2_HIF2a_PANCHill coefficient determined using sigmoidal dose response equation6Float
62Excluded_Points_second_point_HIF2a_PANCFlags 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
63% Activity at 99 uM_second_point_HIF2a_PANC (99μM**)% Activity at the test concentration6Float%
64% Activity at 49.5 uM_second_point_HIF2a_PANC (49.5μM**)% Activity at the test concentration6Float%
65% Activity at 24.75 uM_second_point_HIF2a_PANC (24.75μM**)% Activity at the test concentration6Float%
66% Activity at 12.375 uM_second_point_HIF2a_PANC (12.375μM**)% Activity at the test concentration6Float%
67% Activity at 6.1875 uM_second_point_HIF2a_PANC (6.1875μM**)% Activity at the test concentration6Float%
68% Activity at 3.09375 uM_second_point_HIF2a_PANC (3.09375μM**)% Activity at the test concentration6Float%
69% Activity at 1.546875 uM_second_point_HIF2a_PANC (1.54688μM**)% Activity at the test concentration6Float%
70% Activity at 0.7734375 uM_second_point_HIF2a_PANC (0.773438μM**)% Activity at the test concentration6Float%
71% Activity at 0.3867188 uM_second_point_HIF2a_PANC (0.386719μM**)% Activity at the test concentration6Float%
72% Activity at 0.1933594 uM_second_point_HIF2a_PANC (0.193359μM**)% Activity at the test concentration6Float%
73IC50_Qualifier_1_HIF1aThis 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 value8hypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]String
74IC50_1_HIF1aIC50 value determined using a sigmoidal dose response equation8FloatμM
75Std.Err(IC50)_1_HIF1aStandard Error of the IC50 value8FloatμM
76nH_1_HIF1aHill coefficient determined using sigmoidal dose response equation8Float
77Excluded_Points_first_point_HIF1aFlags 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 99 uM_first_point_HIF1a (99μM**)% Activity at the test concentration8Float%
79% Activity at 49.5 uM_first_point_HIF1a (49.5μM**)% Activity at the test concentration8Float%
80% Activity at 24.75 uM_first_point_HIF1a (24.75μM**)% Activity at the test concentration8Float%
81% Activity at 12.375 uM_first_point_HIF1a (12.375μM**)% Activity at the test concentration8Float%
82% Activity at 6.1875 uM_first_point_HIF1a (6.1875μM**)% Activity at the test concentration8Float%
83% Activity at 3.09375 uM_first_point_HIF1a (3.09375μM**)% Activity at the test concentration8Float%
84% Activity at 1.546875 uM_first_point_HIF1a (1.54688μM**)% Activity at the test concentration8Float%
85% Activity at 0.7734375 uM_first_point_HIF1a (0.773438μM**)% Activity at the test concentration8Float%
86% Activity at 0.3867188 uM_first_point_HIF1a (0.386719μM**)% Activity at the test concentration8Float%
87% Activity at 0.1933594 uM_first_point_HIF1a (0.193359μM**)% Activity at the test concentration8Float%
88IC50_Qualifier_2_HIF1aThis 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 value9hypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]String
89IC50_2_HIF1aIC50 value determined using a sigmoidal dose response equation9FloatμM
90Std.Err(IC50)_2_HIF1aStandard Error of the IC50 value9FloatμM
91nH_2_HIF1aHill coefficient determined using sigmoidal dose response equation9Float
92Excluded_Points_second_point_HIF1aFlags 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 99 uM_second_point_HIF1a (99μM**)% Activity at the test concentration9Float%
94% Activity at 49.5 uM_second_point_HIF1a (49.5μM**)% Activity at the test concentration9Float%
95% Activity at 24.75 uM_second_point_HIF1a (24.75μM**)% Activity at the test concentration9Float%
96% Activity at 12.375 uM_second_point_HIF1a (12.375μM**)% Activity at the test concentration9Float%
97% Activity at 6.1875 uM_second_point_HIF1a (6.1875μM**)% Activity at the test concentration9Float%
98% Activity at 3.09375 uM_second_point_HIF1a (3.09375μM**)% Activity at the test concentration9Float%
99% Activity at 1.546875 uM_second_point_HIF1a (1.54688μM**)% Activity at the test concentration9Float%
100% Activity at 0.7734375 uM_second_point_HIF1a (0.773438μM**)% Activity at the test concentration9Float%
101% Activity at 0.3867188 uM_second_point_HIF1a (0.386719μM**)% Activity at the test concentration9Float%
102% Activity at 0.1933594 uM_second_point_HIF1a (0.193359μM**)% Activity at the test concentration9Float%

* Activity Concentration. ** Test Concentration. § Panel component ID.
Additional Information
Grant Number: 1 R03 DA033980-01A1

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