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BioAssay: AID 588773

Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition and selectivity of HTS compounds in a complex proteome

Name: Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition and selectivity of HTS compounds in a complex proteome. ..more
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 Tested Compounds
 Tested Compounds
All(12)
 
 
Inactive(12)
 
 
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 Tested Substances
All(12)
 
 
Inactive(12)
 
 
AID: 588773
Data Source: The Scripps Research Institute Molecular Screening Center (pPAFAH_INH_FLUO_GELBASEDABPP_SEL_HTS)
BioAssay Type: Panel
Depositor Category: NIH Molecular Libraries Probe Production Network, Assay Provider
Deposit Date: 2011-11-03

Data Table ( Complete ):           View All Data
Tested Compounds:
Related Experiments
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AIDNameTypeProbeComment
463082Fluorescence polarization-based primary biochemical high throughput screening assay to identify inhibitors of the plasma platelet activating factor acetylhydrolase (pPAFAH)Screening depositor-specified cross reference: Primary screen (pPAFAH inhibitors in singlicate)
463092Summary of probe development efforts to identify inhibitors of the plasma platelet activating factor acetylhydrolase (pPAFAH)Summary1 depositor-specified cross reference: Summary (pPAFAH inhibitors)
463230Fluorescence polarization-based biochemical high throughput confirmation assay for inhibitors of the plasma platelet activating factor acetylhydrolase (pPAFAH; PLA2G7)Screening depositor-specified cross reference: Confirmation screen (pPAFAH inhibitors in triplicate)
588474Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of pPAFAHOther depositor-specified cross reference: ABPP Screen (pPAFAH inhibitors in singlicate)
588785Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: LC-MS/MS-based biochemical ABPP-MudPIT assay to determine selectivity of test compounds in the mouse brain membrane proteomeOther depositor-specified cross reference
588787Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: LC-MS/MS-based biochemical ABPP-MudPIT assay to determine selectivity of test compounds in the mouse brain soluble proteomeOther depositor-specified cross reference
588788Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: LC-MS/MS-based biochemical assay to determine binding mode of test compoundsOther depositor-specified cross reference
588789Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of pPAFAH in vivoOther depositor-specified cross reference
588817Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of pPAFAH in situOther depositor-specified cross reference
588823Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of pPAFAH and selectivity analysis in vivoOther depositor-specified cross reference
492956Fluorescence polarization-based primary biochemical high throughput screening assay to identify inhibitors of human platelet activating factor acetylhydrolase 2 (PAFAH2)Screening same project related to Summary assay
588766Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based dose response biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of human pPAFAHConfirmatory same project related to Summary assay
588767Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of PAFAH2Other same project related to Summary assay
588768Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compoundsConfirmatory same project related to Summary assay
588769Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based dose response biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) assay for HTS compoundsConfirmatory same project related to Summary assay
588770Late stage assay provider results from the probe development effort to identify inhibitors of pPAFAH: fluorescence-based dose-response biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) assay for SAR compoundsConfirmatory same project related to Summary assay
588774Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition and selectivity of SAR compounds in a complex proteomeOther same project related to Summary assay
Description:
Source (MLPCN Center Name): The Scripps Research Institute Molecular Screening Center (SRIMSC)
Center Affiliation: The Scripps Research Institute (TSRI)
Assay Providers: Brian Bahnson (Univ. of Delaware); Benjamin Cravatt, (TSRI)
Network: Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1R01HL084366
Grant Proposal PI: Brian Bahnson
External Assay ID: pPAFAH_INH_FLUO_GELBASEDABPP_SEL_HTS

Name: Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition and selectivity of HTS compounds in a complex proteome.

Description:

This project aims to develop specific inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH), and three associated members of the serine hydrolase family of enzymes-PAFAH2, PAFAH1b2, and PAFAH1b3. pPAFAH, an enzyme linked to the inflammatory pathways involved in atherosclerosis, asthma, anaphylactic shock, and other allergic reactions (1,2), is a lipoprotein-associated group VIIA phospholipase A2 that reduces the levels of the signaling molecule platelet activating factor (PAF) (3,4), a potent pro-inflammatory phospholipid signaling molecule (5), and other pro-inflammatory agents, such as oxidized phospholipids, through hydrolysis. A large number of studies have been published over the years since pPAFAH was first discovered linking an increase in pPAFAH concentration and/or activity to an increased risk of various cardiovascular diseases (6,7). The biological function of pPAFAH in the development of coronary heart diseases (CHD) is controversial, with both anti- and pro-inflammatory roles attributed to it (8,9). Dr. Bahnson and colleagues recently reported the first high-resolution crystal structure of the pPAFAH enzyme (10), and would like to expand their studies to co-crystallize pPAFAH with substrate-mimetic inhibitors to further define the active site and substrate specificity of pPAFAH. While one selective pPAFAH inhibitor has been reported (11), its properties are not suitable for the proposed studies. Given the complex biology of the pPAFAH enzymes, a complete characterization of their patho/physiological roles in lipid metabolism is necessary to maximize the success of therapeutic intervention. Towards this goal, development of selective inhibitors would significantly advance our understanding of these enzymes' substrate specificity and contribution to inflammatory disease processes including atherosclerosis, asthma, and rheumatoid arthritis. Pan-PAFAH inhibitors might be of heightened therapeutic value.

References:

1. Karasawa, K., Harada, A., Satoh, N., Inoue, K., and Setaka, M. (2003) Plasma platelet activating factor-acetylhydrolase (PAF-AH), Prog Lipid Res 42, 93-114.
2. Leitinger, N. (2005) Oxidized phospholipids as triggers of inflammation in atherosclerosis, Molecular Nutrition & Food Research 49, 1063-1071.
3. Blank, M. L., Lee, T., Fitzgerald, V., and Snyder, F. (1981) A specific acetylhydrolase for 1-alkyl-2- acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid), J Biol Chem 256, 175-178.
4. Farr, R. S., Cox, C. P., Wardlow, M. L., and Jorgensen, R. (1980) Preliminary studies of an acid labile factor (ALF) in human sera that inactivates platelet-activating factor (PAF), Clin Immunol Immunopathol 15, 318-330.
5. Zimmerman, G. A., McIntyre, T. M., Prescott, S. M., and Stafforini, D. M. (2002) The plateletactivating factor signaling system and its regulators in syndromes of inflammation and thrombosis, Crit Care Med 30, S294-301.
6. Anderson, J. L. (2008) Lipoprotein-associated phospholipase A2: an independent predictor of coronary artery disease events in primary and secondary prevention, Am J Cardiol 101, 23F-33F.
7. Sudhir, K. (2005) Clinical review: Lipoprotein-associated phospholipase A2, a novel inflammatory biomarker and independent risk predictor for cardiovascular disease, J Clin Endocrinol Metab 90, 3100-3105.
8. Wilensky, R. L., and Macphee, C. H. (2009) Lipoprotein-associated phospholipase A(2) and atherosclerosis, Curr Opin Lipidol 20, 415-420.
9. Karabina, S. A., and Ninio, E. (2006) Plasma PAF-acetylhydrolase: an unfulfilled promise?, Biochim Biophys Acta 1761, 1351-1358.
10. Samanta, U., and Bahnson, B. J. (2008) Crystal structure of human plasma platelet-activating factor acetylhydrolase: structural implication to lipoprotein binding and catalysis, J Biol Chem 283, 31617-31624.
11. Blackie, J. A., Bloomer, J. C., Brown, M. J. B., Cheng, H. Y., Hammond, B., Hickey, D. M. B., Ife, R. J., Leach, C. A., Lewis, V. A., Macphee, C. H., Milliner, K. J., Moores, K. E., Pinto, I. L., Smith, S. A., Stansfield, I. G., Stanway, S. J., Taylor, M. A., and Theobald, C. J. (2003) The identification of clinical candidate SB-480848: A potent inhibitor of lipoprotein-associated phospholipase A(2), Bioorganic & Medicinal Chemistry Letters 13, 1067-1070.

Keywords:

late stage, late stage AID, assay provider, low throughput, secondary, PLA2G7, pPAFAH, serine hydrolase, platelet activating factor acetylhydrolase, inflammation, atherosclerosis, liquids, fluorescence, competitive activity-based protein profiling, ABPP, gel-based, inhibitor, selectivity, rhodamine-conjugated fluorophosphonate, FP-Rh, Scripps, The Scripps Research Institute Molecular Screening Center, SRIMSC, Molecular Libraries Probe Production Centers Network, MLPCN
Panel Information
Targets
    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescriptionAdditional Information
ActiveInactive
1pPAFAH12Phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) [Mus musculus] [gi:14715116]
Taxonomy id: 10090
Gene id: 27226
2FAAH111fatty acid amide hydrolase [Mus musculus] [gi:123253900]
Taxonomy id: 10090
Gene id: 14073
3ABHD312abhydrolase domain-containing protein 3 [Mus musculus] [gi:19527360]
Taxonomy id: 10090
Gene id: 106861
4ABHD412Abhydrolase domain containing 4 [Mus musculus] [gi:17028430]
Taxonomy id: 10090
Gene id: 105501
5MAGL12RecName: Full=Monoglyceride lipase; Short=MGL; AltName: Full=Monoacylglycerol lipase; Short=MAGL [gi:47117040]
Taxonomy id: 10090
Gene id: 23945
6ABHD612Abhydrolase domain containing 6 [Mus musculus] [gi:20073260]
Taxonomy id: 10090
Gene id: 66082
7MW 32 kDa12
8MW 30 kDa12
9LYPLA212lysophospholipase 2 [Mus musculus] [gi:123122209]
Taxonomy id: 10090
Gene id: 26394
10LYPLA112Lypla1 [Mus musculus] [gi:71059731]
Taxonomy id: 10090
Gene id: 18777

§ Panel component ID.
Protocol
Assay Overview:
The purpose of this assay is to determine whether cherry picked HTS hit compounds active in a previous assay, AID 588474 [Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of pPAFAH], can inhibit pPAFAH in a gel-based competitive activity-based proteomic profiling (ABPP) assay and to assess compound selectivity in a complex proteome. Test compound is incubated with recombinantly-expressed target enzyme pPAFAH (pPAFAH assay) or serine hydrolase (potential anti-target) rich complex proteome (anti-target assay) followed by reaction with a rhodamine-conjugated fluorophosphonate (FP-Rh) activity-based probe. The reaction products are separated by SDS-PAGE and visualized in-gel using a flatbed fluorescence scanner. The percentage activity remaining is determined by measuring the integrated optical density (IOD) of the bands. As designed, test compounds that act as pPAFAH or anti-target inhibitors will prevent enzyme-probe interactions, thereby decreasing the proportion of bound fluorescent probe, giving lower fluorescence intensity in the band in the gel. Percent inhibition is calculated relative to a DMSO (no compound) control.
Protocol Summary:
pPAFAH Assay:
Recombinant mouse pPAFAH (50 uL of 0.25 mg/mL membrane proteome preparation from transiently transfected 293T Hek cells overexpressing pPAFAH) in Dulbecco's PBS (DPBS) was treated with test compound (10, 1, or 0.1 uM final concentration; 1 uL of a 50x stock in DMSO) or DMSO (1 uL) for 30 minutes at 37 C. FP-Rh (1 uL of a 50 uM solution in DMSO; 1 uM final concentration) was added, and the reaction was incubated for 30 minutes at 37 C, quenched with an equal volume of 2x SDS-PAGE loading buffer (reducing), separated by SDS-PAGE, and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the pPAFAH band relative to a DMSO-only (no compound) control.
Anti-target Assay:
Mouse brain membrane proteome (50 uL of 1 mg/mL) in Dulbecco's PBS (DPBS) was treated with test compound (10, 1, or 0.1 uM final concentration; 1 uL of a 50x stock in DMSO) or DMSO (1 uL) for 30 minutes at 37 C. FP-Rh (1 uL of a 25 uM solution in DMSO; 1 uM final concentration) was added, and the reaction was incubated for 30 minutes at 37 C, quenched with an equal volume of 2x SDS-PAGE loading buffer (reducing), separated by SDS-PAGE, and visualized by in-gel fluorescent scanning. The percentage activity remaining for each anti-target (fatty acid amide hydrolase [FAAH], monoacylglycerol lipase [MAGL], abhydrolase domain-containing proteins 3, 4, and 6 [ABHD3, ABHD4, ABHD6], lysophospholipases 1 and 2 [LYPLA1, LYPLA2], and unidentified proteins with molecular weight [MW] of 32kDa and 30kDa) was determined by measuring the integrated optical density of the individual protein bands relative to a DMSO-only (no compound) control.
%_Inhibition = ( 1 - ( IOD_Test_Compound - IOD_Low_Control ) / ( IOD_High_Control - IOD_Low_Control ) ) * 100
Where:
Test_Compound is defined as target or anti-target enzyme treated with test compound.
High_Control is defined as target or anti-target enzyme treated with DMSO only (no compound).
Low_Control is defined as background in a blank region of the gel.
Fold_selectivity > [Conc_<50%_INH_Anti-target] / [Conc_>=50%_INH_target]
Where:
[Conc_<50%_INH_Anti-target] is the test compound concentration at which less than 50% inhibition of the anti-target is observed.
[Conc_>=50%_INH_target] is the test compound concentration at which greater than or equal to 50% inhibition of target is observed.
If [Conc_>=50%_INH_target] is not determined, then Fold Selectivity is not determined.
If [Conc_<50%_INH_Anti-target] < [Conc_>=50%_INH_target], Fold Selectivity is 0.
PubChem Activity Outcome and Score:
The following applies to each panel in this assay:
Compounds with greater than or equal to 50% inhibition at 0.1 uM test compound concentration were considered active. Compounds with less than 50% inhibition at 0.1 uM test compound concentration were considered inactive.
The reported PubChem Activity Score has been normalized to 100% of the observed value at 0.1 uM.
pPaFAH Score: The PubChem Activity Score range for inactive compounds is 100-0. There are no active compounds.
FAAH: Score: The PubChem Activity Score range for active compounds is 100-100, and for inactive compounds 45-0.
ABHD3 Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
ABHD4 Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
MAGL Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
ABHD6 Score: The PubChem Activity Score range for inactive compounds is 100-0. There are no active compounds.
MW 32 kDa Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
MW 30 kDa Score: The PubChem Activity Score range for inactive compounds is 100-0. There are no active compounds.
LYPLA2 Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
LYPLA1 Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
Overall Outcome and Score:
Compounds with greater than or equal to 50% inhibition of pPAFAH at 0.1 uM test compound concentration and 10-fold or greater selectivity against all anti-targets were considered active. Compounds with less than 50% inhibition at 0.1 uM test compound concentration and/or less than 10-fold selectivity against all anti-targets were considered inactive.
The PubChem Activity Score is assigned a value of 100 for active compounds, and 0 for inactive compounds.
The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
List of Reagents:
Overexpressed pPAFAH 293T membrane proteome (Open Biosystems Accession BC010726, supplied by Assay Provider)
Mouse brain membrane proteome (supplied by Assay Provider)
FP-Rh (supplied by Assay Provider)
DPBS (Cellgro, part 21-030-CV)
Comment
This assay was performed by the assay provider with liquid cherry-picked compounds.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
BAO: assay format: biochemical format: protein format: single protein format
BAO: bioassay specification: assay biosafety level: bsl1
BAO: bioassay specification: assay measurement type: endpoint assay
BAO: bioassay specification: assay readout content: assay readout method: regular screening
BAO: bioassay specification: assay readout content: content readout type: single readout
BAO: bioassay specification: assay stage: secondary: alternate confirmatory
BAO: detection technology: fluorescence: fluorescence intensity
BAO: meta target detail: binding reporter specification: interaction: protein-small molecule
BAO: meta target: molecular target: protein target: enzyme: generic hydrolase
BAO: version: 1.4b1090
From PubChem:
Assay Format: Biochemical
Result Definitions
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TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Outcome [pPAFAH]One of Active, Inactive, or Not Tested1Phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) [Mus musculus]Outcome
2Score [pPAFAH]The BioAssay activity ranking score1Integer
3Inhibition at 10 uM [pPAFAH] (10μM**)Inhibition of recombinant mouse pPAFAH upon 10 uM compound treatment as assessed by gel-based competitive ABPP.1Integer%
4Inhibition at 1 uM [pPAFAH] (1μM**)Inhibition of recombinant mouse pPAFAH upon 1 uM compound treatment as assessed by gel-based competitive ABPP.1Integer%
5Inhibition at 0.1 uM [pPAFAH] (0.1μM**)Inhibition of recombinant mouse pPAFAH upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.1Integer%
6Outcome [FAAH]One of Active, Inactive, or Not Tested2fatty acid amide hydrolase [Mus musculus]Outcome
7Score [FAAH]2Integer
8Inhibition at 10 uM [FAAH] (10μM**)Inhibition of endogenous mouse FAAH upon 10 uM compound treatment as assessed by gel-based competitive ABPP.2Integer%
9Inhibition at 1 uM [FAAH] (1μM**)Inhibition of endogenous mouse FAAH upon 1 uM compound treatment as assessed by gel-based competitive ABPP.2Integer%
10Inhibition at 0.1 uM [FAAH] (0.1μM**)Inhibition of endogenous mouse FAAH upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.2Integer%
11Qualifier [FAAH]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.2String
12Fold Selectivity [FAAH]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target FAAH is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.2Integerratio
13Outcome [ABHD3]One of Active, Inactive, or Not Tested3abhydrolase domain-containing protein 3 [Mus musculus]Outcome
14Score [ABHD3]The BioAssay activity ranking score3Integer
15Inhibition at 10 uM [ABHD3] (10μM**)Inhibition of endogenous mouse ABHD3 upon 10 uM compound treatment as assessed by gel-based competitive ABPP.3Integer%
16Inhibition at 1 uM [ABHD3] (1μM**)Inhibition of endogenous mouse ABHD3 upon 1 uM compound treatment as assessed by gel-based competitive ABPP.3Integer%
17Inhibition at 0.1 uM [ABHD3] (0.1μM**)Inhibition of endogenous mouse ABHD3 upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.3Integer%
18Qualifier [ABHD3]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.3String
19Fold Selectivity [ABHD3]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target ABHD3 is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.3Integerratio
20Outcome [ABHD4]One of Active, Inactive, or Not Tested4Abhydrolase domain containing 4 [Mus musculus]Outcome
21Score [ABHD4]The BioAssay activity ranking score4Integer
22Inhibition at 10 uM [ABHD4] (10μM**)Inhibition of endogenous mouse ABHD4 upon 10 uM compound treatment as assessed by gel-based competitive ABPP.4Integer%
23Inhibition at 1 uM [ABHD4] (1μM**)Inhibition of endogenous mouse ABHD4 upon 1 uM compound treatment as assessed by gel-based competitive ABPP.4Integer%
24Inhibition at 0.1 uM [ABHD4] (0.1μM**)Inhibition of endogenous mouse ABHD4 upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.4Integer%
25Qualifier [ABHD4]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.4String
26Fold Selectivity [ABHD4]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target ABHD4 is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.4Integerratio
27Outcome [MAGL]One of Active, Inactive, or Not Tested5RecName: Full=Monoglyceride lipase; Short=MGL; AltName: Full=Monoacylglycerol lipase; Short=MAGLOutcome
28Score [MAGL]The BioAssay activity ranking score5Integer
29Inhibition at 10 uM [MAGL] (10μM**)Inhibition of endogenous mouse MAGL upon 10 uM compound treatment as assessed by gel-based competitive ABPP.5Integer%
30Inhibition at 1 uM [MAGL] (1μM**)Inhibition of endogenous mouse MAGL upon 1 uM compound treatment as assessed by gel-based competitive ABPP.5Integer%
31Inhibition at 0.1 uM [MAGL] (0.1μM**)Inhibition of endogenous mouse MAGL upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.5Integer%
32Qualifier [MAGL]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.5String
33Fold Selectivity [MAGL]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target MAGL is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.5Integerratio
34Outcome [ABHD6]One of Active, Inactive, or Not Tested6Abhydrolase domain containing 6 [Mus musculus]Outcome
35Score [ABHD6]The BioAssay activity ranking score6Integer
36Inhibition at 10 uM [ABHD6] (10μM**)Inhibition of endogenous mouse ABHD6 upon 10 uM compound treatment as assessed by gel-based competitive ABPP.6Integer%
37Inhibition at 1 uM [ABHD6] (1μM**)Inhibition of endogenous mouse ABHD6 upon 1 uM compound treatment as assessed by gel-based competitive ABPP.6Integer%
38Inhibition at 0.1 uM [ABHD6] (0.1μM**)Inhibition of endogenous mouse ABHD6 upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.6Integer%
39Qualifier [ABHD6]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.6String
40Fold Selectivity [ABHD6]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target ABHD6 is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.6Integerratio
41Outcome [MW 32 kDa]One of Active, Inactive, or Not Tested7Outcome
42Score [MW 32]The BioAssay activity ranking score7Integer
43Inhibition at 10 uM [MW 32 kDa] (10μM**)Inhibition of endogenous mouse anti-target with MW = 32kDa upon 10 uM compound treatment as assessed by gel-based competitive ABPP.7Integer%
44Inhibition at 1 uM [MW 32 kDa] (1μM**)Inhibition of endogenous mouse anti-target with MW = 32kDa upon 1 uM compound treatment as assessed by gel-based competitive ABPP.7Integer%
45Inhibition at 0.1 uM [MW 32 kDa] (0.1μM**)Inhibition of endogenous mouse anti-target with MW = 32kDa upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.7Integer%
46Qualifier [MW 32 kDa]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.7String
47Fold Selectivity [MW 32 kDa]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target with MW = 32kDa is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.7Integerratio
48Outcome [MW 30 kDa]One of Active, Inactive, or Not Tested8Outcome
49Score [MW 30 kDa]The BioAssay activity ranking score8Integer
50Inhibition at 10 uM [MW 30 kDa] (10μM**)Inhibition of endogenous mouse anti-target with MW = 30kDa upon 10 uM compound treatment as assessed by gel-based competitive ABPP.8Integer%
51Inhibition at 1 uM [MW 30 kDa] (1μM**)Inhibition of endogenous mouse anti-target with MW = 30kDa upon 1 uM compound treatment as assessed by gel-based competitive ABPP.8Integer%
52Inhibition at 0.1 uM [MW 30 kDa] (0.1μM**)Inhibition of endogenous mouse anti-target with MW = 30kDa upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.8Integer%
53Qualifier [MW 30 kDa]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.8String
54Fold Selectivity [MW 30 kDa]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target with MW = 30kDa is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.8Integerratio
55Outcome [LYPLA2]One of Active, Inactive, or Not Tested9lysophospholipase 2 [Mus musculus]Outcome
56Score [LYPLA2]The BioAssay activity ranking score9Integer
57Inhibition at 10 uM [LYPLA2] (10μM**)Inhibition of endogenous mouse LYPLA2 upon 10 uM compound treatment as assessed by gel-based competitive ABPP.9Integer%
58Inhibition at 1 uM [LYPLA2] (1μM**)Inhibition of endogenous mouse LYPLA2 upon 1 uM compound treatment as assessed by gel-based competitive ABPP.9Integer%
59Inhibition at 0.1 uM [LYPLA2] (0.1μM**)Inhibition of endogenous mouse LYPLA2 upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.9Integer%
60Qualifier [LYPLA2]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.9String
61Fold Selectivity [LYPLA2]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target LYPLA2 is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.9Integerratio
62Outcome [LYPLA1]One of Active, Inactive, or Not Tested10Lypla1 [Mus musculus]Outcome
63Score [LYPLA1]The BioAssay activity ranking score10Integer
64Inhibition at 10 uM [LYPLA1] (10μM**)Inhibition of endogenous mouse LYPLA1 upon 10 uM compound treatment as assessed by gel-based competitive ABPP.10Integer%
65Inhibition at 1 uM [LYPLA1] (1μM**)Inhibition of endogenous mouse LYPLA1 upon 1 uM compound treatment as assessed by gel-based competitive ABPP.10Integer%
66Inhibition at 0.1 uM [LYPLA1] (0.1μM**)Inhibition of endogenous mouse LYPLA1 upon 0.1 uM compound treatment as assessed by gel-based competitive ABPP.10Integer%
67Qualifier [LYPLA1]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.10String
68Fold Selectivity [LYPLA1]The ratio of the test compound concentration at which less than 50% inhibition of the anti-target LYPLA1 is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.10Integerratio
69Anti-target Count at 10 uMThe total number of observed anti-targets with greater than or equal to 50% inhibition at 10 uM test compound concentration as assessed by gel-based ABPPInteger
70Anti-target Count at 1 uMThe total number of observed anti-targets with greater than or equal to 50% inhibition at 1 uM test compound concentration as assessed by gel-based ABPPInteger
71Anti-target Count at 0.1 uMThe total number of observed anti-targets with greater than or equal to 50% inhibition at 0.1 uM test compound concentration as assessed by gel-based ABPPInteger
72QualifierQualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.String
73Overall Fold SelectivityThe smallest ratio of the test compound concentration at which less than 50% inhibition of the anti-target (as calcuated for FAAH, ABHD3, ABHD4, MAGL, ABHD6, 32kDa, 30kDa, LYPLA2, and LYPLA1) is observed over the test compound concentration at which greater than or equal to 50% inhibition of pPAFAH is observed.Integerratio

** Test Concentration. § Panel component ID.
Additional Information
Grant Number: 1R01HL084366

Classification
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