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BioAssay: AID 602339

Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis

Name: Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis. ..more
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AID: 602339
Data Source: The Scripps Research Institute Molecular Screening Center (DAGLB_INH_LCMS_ABPPSILAC)
BioAssay Type: Panel
Depositor Category: NIH Molecular Libraries Probe Production Network, Assay Provider
BioAssay Version:
Deposit Date: 2012-03-09
Hold-until Date: 2012-10-12
Modify Date: 2012-10-12

Data Table ( Complete ):           Active    All
BioActive Compound: 1
Depositor Specified Assays
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AIDNameTypeProbeComment
504411Fluorescence-based primary biochemical high throughput screening assay to identify inhibitors of human diacylglycerol lipase, beta (DAGLB)screening Primary screen (DAGLB inhibitors in singlicate)
504420Summary of the probe development efforts to identify inhibitors of human diacylglycerol lipase, beta (DAGLB)summary3 Summary (DAGLB inhibitors)
504445Fluorescence-based biochemical high throughput confirmation assay for inhibitors of human diacylglycerol lipase, beta (DAGLB)screening ABPP screen (DAGLb inhibitors in triplicate)
602403Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of recombinant antitarget DAGLa in vitroother
602415Assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): LC/MS-based biochemical inhibition of overexpressed DAGLb substrate turnover in vitroother
624039Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): fluorescence-based dose-response biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of antitarget ABHD6 in vitro, set 2confirmatory
624041Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of mouse liver ABHD6 in vivoother
624077Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of mouse liver ABHD6 in vivo upon oral compound administrationother
624468Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): LCMS-based biochemical dose response assayconfirmatory
624472Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): fluorescence-based biochemical gel-based competitive Activity-Based Protein Profiling (ABPP) inhibition of DAGLb by enantiomers of KT116other
Description:
Source (MLPCN Center Name): The Scripps Research Institute Molecular Screening Center (SRIMSC)
Affiliation: The Scripps Research Institute, TSRI
Assay Provider: Benjamin Cravatt, The Scripps Research Institute (TSRI)
Network: Molecular Library Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R01 DA025285
Grant Proposal PI: Benjamin Cravatt, The Scripps Research Institute (TSRI)
External Assay ID: DAGLB_INH_LCMS_ABPPSILAC

Name: Late stage assay provider results from the probe development effort to identify inhibitors of diacylglycerol lipase, beta (DAGLb): LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis.

Description:

Endocannabinoids (ECs) represent a unique group of lipids that function as chemical messengers in the nervous system. To date, the two principle ECs identified in mammals are N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoyl-glycerol (2-AG). They have been implicated in various physiological and pathological functions including appetite, pain, sensation, memory, and addiction (1). Unlike traditional neurotransmitters, which are stored in vesicles, ECs are synthesized and released on demand, and then rapidly degraded to terminate signaling. Thus, the metabolic pathways that govern EC turnover are critical in determining the magnitude and duration of neuronal signaling events (2). Endocannabinoid biosynthesis, in contrast to degradation, is poorly understood. Recently, two serine hydrolases, DAGL-a and -B, were cloned and found to selectively cleave sn-1 acyl chains from diacylglycerols (DAG) to generate 2-AG in vitro (3). Their function in the nervous system was validated in vivo by the generation of DAGL-a and -B knock-out mice (4, 5). However, it is still unclear to what extent DAGL-a/B catalytic activity contributes to 2-AG-mediated signaling. The development of potent and selective inhibitors would offer a means to perturb DAGL-a/B activity in a selective, reversible, and temporally-controlled manner. Given the non-selective nature of current DAGL-a/B inhibitors (6), specific chemical probes would serve as invaluable tools to delineate DAGL-a/B function in 2-AG signaling networks of the brain.

References:

1. Di Marzo, V. (2008) Targeting the endocannabinoid system: to enhance or reduce?, Nat Rev Drug Discov 7, 438-455.
2. Ahn, K., McKinney, M. K., and Cravatt, B. F. (2008) Enzymatic pathways that regulate endocannabinoid signaling in the nervous system, Chem Rev 108, 1687-1707.
3. Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., Matias, I., Schiano-Moriello, A., Paul, P., Williams, E. J., Gangadharan, U., Hobbs, C., Di Marzo, V., and Doherty, P. (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain, J Cell Biol 163, 463-468.
4. Gao, Y., Vasilyev, D. V., Goncalves, M. B., Howell, F. V., Hobbs, C., Reisenberg, M., Shen, R., Zhang, M. Y., Strassle, B. W., Lu, P., Mark, L., Piesla, M. J., Deng, K., Kouranova, E. V., Ring, R. H., Whiteside, G. T., Bates, B., Walsh, F. S., Williams, G., Pangalos, M. N., Samad, T. A., and Doherty, P. (2010) Loss of Retrograde Endocannabinoid Signaling and Reduced Adult Neurogenesis in Diacylglycerol Lipase Knock-out Mice, J Neurosci 30, 2017-2024.
5. Tanimura, A., Yamazaki, M., Hashimotodani, Y., Uchigashima, M., Kawata, S., Abe, M., Kita, Y., Hashimoto, K., Shimizu, T., Watanabe, M., Sakimura, K., and Kano, M. (2010) The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase +/- Mediates Retrograde Suppression of Synaptic Transmission, Neuron 65, 320-327.
6. Hoover, H. S., Blankman, J. L., Niessen, S., and Cravatt, B. F. (2008) Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling, Bioorganic & Medicinal Chemistry Letters 18, 5838-5841.

Keywords:

late stage, late stage AID, assay provider, powders, counterscreen, diacylglycerol lipase, diacylglycerol lipase-beta, DAGL, DAGL-beta, DAGLB, hydrolase, serine hydrolase, appetite, pain, sensation, memory, addiction, liquid chromatography, LC, tandem mass spectrometry, MS/MS, activity-based protein profiling, ABPP, stable isotope labeling with amino acids in cell culture, SILAC, ABPP-SILAC, inhibitor, inhibition, fluorophosphonate-biotin, FP-biotin, in situ, Neuro-2A, Scripps, Scripps Research Institute Molecular Screening Center, SRIMSC, Molecular Libraries Probe Production Centers Network, MLPCN
Panel Information
Targets
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescriptionAdditional Information
ActiveInactive
1Plat1tissue-type plasminogen activator preproprotein [Mus musculus] [gi:170763477]
Taxonomy id: 10090
Gene id: 18791
2Lonp11lon protease homolog, mitochondrial precursor [Mus musculus] [gi:116089322]
Taxonomy id: 10090
Gene id: 74142
3Ctsa1lysosomal protective protein isoform b precursor [Mus musculus] [gi:84042523]
Taxonomy id: 10090
Gene id: 19025
4Lyplal11lysophospholipase-like protein 1 [Mus musculus] [gi:227496223]
Taxonomy id: 10090
Gene id: 226791
5Scpep11retinoid-inducible serine carboxypeptidase precursor [Mus musculus] [gi:253970508]
Taxonomy id: 10090
Gene id: 74617
6Qrsl11glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial [Mus musculus] [gi:124486688]
Taxonomy id: 10090
Gene id: 76563
7Pnpla71patatin-like phospholipase domain-containing protein 7 [Mus musculus] [gi:225007615]
Taxonomy id: 10090
Gene id: 241274
8Abhd111abhydrolase domain-containing protein 11 isoform 1 [Mus musculus] [gi:21644577]
Taxonomy id: 10090
Gene id: 68758
9Ache1acetylcholinesterase precursor [Mus musculus] [gi:13928664]
Taxonomy id: 10090
Gene id: 11423
10Serhl1serine hydrolase-like protein [Mus musculus] [gi:13443008]
Taxonomy id: 10090
Gene id: 68607
11Ppt21lysosomal thioesterase PPT2 precursor [Mus musculus] [gi:9506985]
Taxonomy id: 10090
Gene id: 54397
12Acot21acyl-coenzyme A thioesterase 2, mitochondrial precursor [Mus musculus] [gi:238624114]
Taxonomy id: 10090
Gene id: 171210
13Bat51abhydrolase domain-containing protein 16A [Mus musculus] [gi:30519896]
Taxonomy id: 10090
Gene id: 193742
14Htra21fatty acid synthase [Mus musculus] [gi:93102409]
Taxonomy id: 10090
Gene id: 64704
15Kiaa13631neutral cholesterol ester hydrolase 1 [Mus musculus] [gi:30520239]
Taxonomy id: 10090
Gene id: 320024
16Pnpla81calcium-independent phospholipase A2-gamma [Mus musculus] [gi:118130807]
Taxonomy id: 10090
Gene id: 67452
17Pnpla61neuropathy target esterase isoform 1 [Mus musculus] [gi:390608665]
Taxonomy id: 10090
Gene id: 50767
18Fam108c1abhydrolase domain-containing protein FAM108C1 [Mus musculus] [gi:158186616]
Taxonomy id: 10090
Gene id: 70178
19D230012E17Rik1GPI inositol-deacylase [Mus musculus] [gi:254028203]
Taxonomy id: 10090
Gene id: 241062
20Dpp71dipeptidyl peptidase 2 precursor [Mus musculus] [gi:31981425]
Taxonomy id: 10090
Gene id: 83768
21Lactb1serine beta-lactamase-like protein LACTB, mitochondrial precursor [Mus musculus] [gi:13507666]
Taxonomy id: 10090
Gene id: 80907
22Fam108b1abhydrolase domain-containing protein FAM108B1 precursor [Mus musculus] [gi:38142456]
Taxonomy id: 10090
Gene id: 226016
23Abhd121monoacylglycerol lipase ABHD12 [Mus musculus] [gi:159110817]
Taxonomy id: 10090
Gene id: 76192
24Esd1S-formylglutathione hydrolase [Mus musculus] [gi:13937355]
Taxonomy id: 10090
Gene id: 13885
25Lipe1hormone-sensitive lipase isoform 2 [Mus musculus] [gi:87239972]
Taxonomy id: 10090
Gene id: 16890
26Fasn1fatty acid synthase [Mus musculus] [gi:93102409]
Taxonomy id: 10090
Gene id: 14104
27Pme11protein phosphatase methylesterase 1 [Mus musculus] [gi:30794138]
Taxonomy id: 10090
Gene id: 72590
28Parl1presenilins-associated rhomboid-like protein, mitochondrial precursor [Mus musculus] [gi:54261813]
Taxonomy id: 10090
Gene id: 381038
29Faah1fatty acid amide hydrolase [Mus musculus] [gi:123253900]
Taxonomy id: 10090
Gene id: 14073
30Iah11isoamyl acetate-hydrolyzing esterase 1 homolog [Mus musculus] [gi:27754071]
Taxonomy id: 10090
Gene id: 67732
31Pafah1b21platelet-activating factor acetylhydrolase IB subunit beta [Mus musculus] [gi:40254624]
Taxonomy id: 10090
Gene id: 18475
32Abhd101abhydrolase domain-containing protein 10, mitochondrial precursor [Mus musculus] [gi:269784760]
Taxonomy id: 10090
Gene id: 213012
33Lypla21acyl-protein thioesterase 2 [Mus musculus] [gi:7242156]
Taxonomy id: 10090
Gene id: 26394
34Prep1prolyl endopeptidase [Mus musculus] [gi:6755152]
Taxonomy id: 10090
Gene id: 19072
35Prepl1prolyl endopeptidase-like isoform a [Mus musculus] [gi:254939518]
Taxonomy id: 10090
Gene id: 213760
36Pafah1b31platelet-activating factor acetylhydrolase IB subunit gamma [Mus musculus] [gi:6679201]
Taxonomy id: 10090
Gene id: 18476
37Ddhd11phospholipase DDHD1 isoform 2 [Mus musculus] [gi:111955224]
Taxonomy id: 10090
Gene id: 114874
38Pafah21platelet-activating factor acetylhydrolase 2, cytoplasmic [Mus musculus] [gi:225579137]
Taxonomy id: 10090
Gene id: 100163
39Apeh1Acylpeptide hydrolase [Mus musculus] [gi:19343726]
Taxonomy id: 10090
Gene id: 235606
40Lypla31group XV phospholipase A2 precursor [Mus musculus] [gi:19527008]
Taxonomy id: 10090
Gene id: 192654
41Abhd41abhydrolase domain-containing protein 4 isoform 1 [Mus musculus] [gi:326937491]
Taxonomy id: 10090
Gene id: 105501
42Dpp91dipeptidyl peptidase 9 [Mus musculus] [gi:255003757]
Taxonomy id: 10090
Gene id: 224897
43Lypla11acyl-protein thioesterase 1 [Mus musculus] [gi:6678760]
Taxonomy id: 10090
Gene id: 18777
44Tpp21Tpp2 protein [Mus musculus] [gi:37194903]
Taxonomy id: 10090
Gene id: 22019
45Abhd61monoacylglycerol lipase ABHD6 [Mus musculus] [gi:31560264]
Taxonomy id: 10090
Gene id: 66082
46Daglb1sn1-specific diacylglycerol lipase beta [Mus musculus] [gi:31559956]
Taxonomy id: 10090
Gene id: 231871

§ Panel component ID.
Protocol
Assay Overview:

The purpose of this assay is to determine the selectivity profile of powder samples of test compounds using activity-based protein profiling (ABPP) in combination with stable isotope labeling with amino acids in cell culture (SILAC). In this assay, cultured Neuro-2A cells are metabolically labeled with heavy or light amino acids. Heavy and light cells are treated with test compound and DMSO, respectively, in situ. Cells are lysed, proteomes are treated with the serine-hydrolase-specific activity-based fluorophosphonate-biotin (FP-biotin) affinity probe, and combined in a 1:1 (w/w) ratio. Biotinylated proteins are enriched, trypsinized, and analyzed by multi-dimensional liquid chromatography tandem mass spectrometery LC/LC-MS/MS (MudPIT). Inhibition of target and anti-target activity is quantified by comparing intensities of light and heavy peptide peaks. As designed, compounds that act as inhibitors will block FP-biotin labeling, reducing enrichment in the inhibitor-treated (heavy) sample relative to the DMSO-treated (light) sample, giving a smaller heavy/light ratio for each protein. Proteins not targeted by inhibitors would be expected to have a ratio of 1.

Protocol Summary:

Sample Preparation. Neuro-2A murine neuroblastoma cells were initially grown for 10 passages in either light or heavy SILAC DMEM medium supplemented with 10% dialyzed FCS and 2 mM L-glutamine. Light medium was supplemented with 100 ug/mL L-arginine and 100 ug/mL L-lysine. Heavy medium was supplemented with 100 ug/mL [13C615N4]-L-Arginine and 100 ug/mL [13C615N2]-L-Lysine. Heavy cells (in 10 mL medium) were treated with test compound KT172 (SID125269120, CID53364485) (10 uL of a 1000x stock in DMSO; 25 nM final concentration) and light cells were treated with DMSO (10 uL) for 4 hours at 37 C. Cells were washed with DPBS (4x), harvested, and homogenized by sonication in DPBS. The soluble and membrane fractions were isolated by centrifugation (100K x g, 45 minutes) and the protein concentration for each fraction was adjusted to 2 mg/mL with DPBS. The light and heavy proteomes were labeled with the activity-based affinity probe FP-biotin (500 uL total reaction volume, 10 uM final concentration) for 2 hours at 25 C. After incubation, light and heavy proteomes were mixed in 1:1 ratio, and the membrane proteomes were additionally solubilized with 1% Triton-X100. Samples were desalted over PD10 columns (GE Healthcare) in DPBS, and biotinylated proteins enriched with streptavidin beads (50 uL beads; conditions: 1 hour, 25 C 0.5% SDS in DPBS). The beads were washed with 1% SDS in DPBS (1x), 6 M urea (1x), and DPBS (2x), then resuspended in in 6 M urea (150 uL), reduced with 5 mM TCEP for 20 minutes, and alkylated with 10 mM iodoacetamide for 30 minutes at 25 C in the dark. The urea concentration was reduced to 2 M with 2x volume DPBS. On-bead digestions were performed for 12 hours at 37 C with sequence-grade modified trypsin (Promega; 2 ug) in the presence of 2 mM CaCl2. Peptide samples were acidified to a final concentration of 5% (v/v) formic acid and stored at -80 C prior to analysis.

LC-MS/MS analysis. Samples were analyzed by multidimensional liquid chromatography tandem mass spectrometry (MudPIT) using an Agilent 1200-series quaternary pump and Thermo Scientific LTQ-Orbitrap Velos ion trap mass spectrometer. Peptides were eluted in a 5-step MudPIT experiment using 0%, 25%, 50%, 80%, and 100% salt bumps of 500 mM aqueous ammonium acetate and data were collected in data-dependent acquisition mode with dynamic exclusion turned on (20 seconds, repeat of 1). Specifically, one full MS (MS1) scan (400-1800 m/z) was followed by 30 MS2 scans of the most abundant ions. The MS2 spectra data were extracted from the raw file using RAW Xtractor (version 1.9.9.2; publicly available at http://fields.scripps.edu/downloads.php). MS2 spectra data were searched using the ProLuCID algorithm (publicly available at http://fields.scripps.edu/downloads.php) against the latest version of the mouse IPI database concatenated with the reversed database for assessment of false-discovery rates. ProLucid searches allowed for static modification of cysteine residues (+57.02146 due to alkylation), methionine oxidation (+15.9949), mass shifts of labeled amino acids (+10.0083 R, +8.0142 K) and no enzyme specificity. The resulting MS2 spectra matches were assembled into protein identifications and filtered using DTASelect (version 2.0) using the --modstat, --mass, and --trypstat options (applies different statistical models for the analysis of high resolution masses, peptide digestion state, and methionine oxidation state respectively). Ratios of heavy/light (test compound/DMSO) peaks were calculated using in-house software and normalized at the peptide level to the average ratio of all non-serine hydrolase peptides. Reported ratios represent the mean of all unique, quantified peptides per protein and do not include peptides that were >3 standard deviations from the median peptide value. Proteins with less than three peptides per protein ID were not included in the analysis.

Ratio = Average( AUClight / AUCheavy ) calculated for all unique peptides

Where:

AUClight is the area-under-the-curve for the light peptide pair from cells treated with test compound.
AUCheavy is the area-under-the-curve for the heavy peptide pair from cells treated with DMSO.

PubChem Activity Outcome and Score:

The following applies to each panel in this assay:

A compound was considered active for a particular target/anti-target with a light/heavy ratio of less than or equal to 0.5. A compound was considered inactive for a specified target/anti-target with a light/heavy ratio of greater than 0.5.

Overall Outcome and Score:

A compound was considered active if it was active for DAGLb and active for fewer than two anti-target serine hydrolases tested.

The PubChem Activity Score is assigned a value of 100 for active compounds, and 0 for inactive compounds.

The PubChem Activity Score range for active compounds is 100-100. There are no inactive compounds.

List of Reagents:

Neuro-2A murine cells (provided by Assay Provider)
SILAC DMEM media (Thermo 89985)
dialyzed FCS (Gemini 100-108)
1x Glutamine (CellGro 25-005-CI)
L-Arginine (SigmaAldrich A6969)
L-Lysine (SigmaAldrich L9037)
[13C615N4]-L-Arginine (SigmaAldrich 608033)
[13C615N2]-L-Lysine (SigmaAldrich 608041)
DPBS (Cellgro 20-031-CV)
FP-biotin (provided by Assay Provider)
Comment
This assay was performed by the assay provider with powder samples of synthetic compounds.
Categorized Comment
BAO: version: 1.4b1090

BAO: bioassay specification: assay stage: secondary: counter screening

BAO: bioassay specification: assay biosafety level: bsl1

BAO: assay format: biochemical format: protein format: single protein format

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: meta target: molecular target: protein target: enzyme: generic hydrolase

BAO: meta target: biological process target: regulation of molecular function

BAO: meta target detail: binding reporter specification: interaction: protein-small molecule

BAO: detection technology: fluorescence: fluorescence intensity

Result Definitions
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TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Outcome [Plat]One of Active, Inactive, or Not Tested1tissue-type plasminogen activator preproprotein [Mus musculus]Outcome
2Mean Ratio [Plat]Calculated inhibitor-treated/DMSO ratio for Plat as mean for all unique peptides quantified1Floatratio
3Standard Error [Plat]Calculated standard error for mean1Float
4Outcome [Lonp1]One of Active, Inactive, or Not Tested2lon protease homolog, mitochondrial precursor [Mus musculus]Outcome
5Mean Ratio [Lonp1]Calculated inhibitor-treated/DMSO ratio for Lonp1 as mean for all unique peptides quantified2Floatratio
6Standard Error [Lonp1]Calculated standard error for mean2Float
7Outcome [Ctsa]One of Active, Inactive, or Not Tested3lysosomal protective protein isoform b precursor [Mus musculus]Outcome
8Mean Ratio [Ctsa]Calculated inhibitor-treated/DMSO ratio for Ctsa as mean for all unique peptides quantified3Floatratio
9Standard Error [Ctsa]Calculated standard error for mean3Float
10Outcome [Lyplal1]One of Active, Inactive, or Not Tested4lysophospholipase-like protein 1 [Mus musculus]Outcome
11Mean Ratio [Lyplal1]Calculated inhibitor-treated/DMSO ratio for Lyplal1 as mean for all unique peptides quantified4Floatratio
12Standard Error [Lyplal1]Calculated standard error for mean4Float
13Outcome [Scpep1]One of Active, Inactive, or Not Tested5retinoid-inducible serine carboxypeptidase precursor [Mus musculus]Outcome
14Mean Ratio [Scpep1]Calculated inhibitor-treated/DMSO ratio for Scpep1 as mean for all unique peptides quantified5Floatratio
15Standard Error [Scpep1]Calculated standard error for mean5Float
16Outcome [Qrsl1]One of Active, Inactive, or Not Tested6glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial [Mus musculus]Outcome
17Mean Ratio [Qrsl1]Calculated inhibitor-treated/DMSO ratio for Qrsl1 as mean for all unique peptides quantified6Floatratio
18Standard Error [Qrsl1]Calculated standard error for mean6Float
19Outcome [Pnpla7]One of Active, Inactive, or Not Tested7patatin-like phospholipase domain-containing protein 7 [Mus musculus]Outcome
20Mean Ratio [Pnpla7]Calculated inhibitor-treated/DMSO ratio for Pnpla7 as mean for all unique peptides quantified7Floatratio
21Standard Error [Pnpla7]Calculated standard error for mean7Float
22Outcome [Abhd11]One of Active, Inactive, or Not Tested8abhydrolase domain-containing protein 11 isoform 1 [Mus musculus]Outcome
23Mean Ratio [Abhd11]Calculated inhibitor-treated/DMSO ratio for Abhd11 as mean for all unique peptides quantified8Floatratio
24Standard Error [Abhd11]Calculated standard error for mean8Float
25Outcome [Ache]One of Active, Inactive, or Not Tested9acetylcholinesterase precursor [Mus musculus]Outcome
26Mean Ratio [Ache]Calculated inhibitor-treated/DMSO ratio for Ache as mean for all unique peptides quantified9Floatratio
27Standard Error [Ache]Calculated standard error for mean9Float
28Outcome [Serhl]One of Active, Inactive, or Not Tested10serine hydrolase-like protein [Mus musculus]Outcome
29Mean Ratio [Serhl]Calculated inhibitor-treated/DMSO ratio for Serhl as mean for all unique peptides quantified10Floatratio
30Standard Error [Serhl]Calculated standard error for mean10Float
31Outcome [Ppt2]One of Active, Inactive, or Not Tested11lysosomal thioesterase PPT2 precursor [Mus musculus]Outcome
32Mean Ratio [Ppt2]Calculated inhibitor-treated/DMSO ratio for Ppt2 as mean for all unique peptides quantified11Floatratio
33Standard Error [Ppt2]Calculated standard error for mean11Float
34Outcome [Acot2]One of Active, Inactive, or Not Tested12acyl-coenzyme A thioesterase 2, mitochondrial precursor [Mus musculus]Outcome
35Mean Ratio [Acot2]Calculated inhibitor-treated/DMSO ratio for Acot2 as mean for all unique peptides quantified12Floatratio
36Standard Error [Acot2]Calculated standard error for mean12Float
37Outcome [Bat5]One of Active, Inactive, or Not Tested13abhydrolase domain-containing protein 16A [Mus musculus]Outcome
38Mean Ratio [Bat5]Calculated inhibitor-treated/DMSO ratio for Bat5 as mean for all unique peptides quantified13Floatratio
39Standard Error [Bat5]Calculated standard error for mean13Float
40Outcome [Htra2]One of Active, Inactive, or Not Tested14fatty acid synthase [Mus musculus]Outcome
41Mean Ratio [Htra2]Calculated inhibitor-treated/DMSO ratio for HtrA2 as mean for all unique peptides quantified14Floatratio
42Standard Error [Htra2]Calculated standard error for mean14Float
43Outcome [Kiaa1363]One of Active, Inactive, or Not Tested15neutral cholesterol ester hydrolase 1 [Mus musculus]Outcome
44Mean Ratio [Kiaa1363]Calculated inhibitor-treated/DMSO ratio for Kiaa1363 as mean for all unique peptides quantified15Floatratio
45Standard Error [Kiaa1363]Calculated standard error for mean15Float
46Outcome [Pnpla8]One of Active, Inactive, or Not Tested16calcium-independent phospholipase A2-gamma [Mus musculus]Outcome
47Mean Ratio [Pnpla8]Calculated inhibitor-treated/DMSO ratio for Pnpla8 as mean for all unique peptides quantified16Floatratio
48Standard Error [Pnpla8]Calculated standard error for mean16Float
49Outcome [Pnpla6]One of Active, Inactive, or Not Tested17neuropathy target esterase isoform 1 [Mus musculus]Outcome
50Mean Ratio [Pnpla6]Calculated inhibitor-treated/DMSO ratio for Pnpla6 as mean for all unique peptides quantified17Floatratio
51Standard Error [Pnpla6]Calculated standard error for mean17Float
52Outcome [Fam108c]One of Active, Inactive, or Not Tested18abhydrolase domain-containing protein FAM108C1 [Mus musculus]Outcome
53Mean Ratio [Fam108c]Calculated inhibitor-treated/DMSO ratio for Fam108c as mean for all unique peptides quantified18Floatratio
54Standard Error [Fam108c]Calculated standard error for mean18Float
55Outcome [D230012E17Rik]One of Active, Inactive, or Not Tested19GPI inositol-deacylase [Mus musculus]Outcome
56Mean Ratio [D230012E17Rik]Calculated inhibitor-treated/DMSO ratio for D230012E17Rik as mean for all unique peptides quantified19Floatratio
57Standard Error [D230012E17Rik]Calculated standard error for mean19Float
58Outcome [Dpp7]One of Active, Inactive, or Not Tested20dipeptidyl peptidase 2 precursor [Mus musculus]Outcome
59Mean Ratio [Dpp7]Calculated inhibitor-treated/DMSO ratio for Dpp7 as mean for all unique peptides quantified20Floatratio
60Standard Error [Dpp7]Calculated standard error for mean20Float
61Outcome [Lactb]One of Active, Inactive, or Not Tested21serine beta-lactamase-like protein LACTB, mitochondrial precursor [Mus musculus]Outcome
62Mean Ratio [Lactb]Calculated inhibitor-treated/DMSO ratio for Lactb as mean for all unique peptides quantified21Floatratio
63Standard Error [Lactb]Calculated standard error for mean21Float
64Outcome [Fam108b]One of Active, Inactive, or Not Tested22abhydrolase domain-containing protein FAM108B1 precursor [Mus musculus]Outcome
65Mean Ratio [Fam108b]Calculated inhibitor-treated/DMSO ratio for Fam108b as mean for all unique peptides quantified22Floatratio
66Standard Error [Fam108b]Calculated standard error for mean22Float
67Outcome [Abhd12]One of Active, Inactive, or Not Tested23monoacylglycerol lipase ABHD12 [Mus musculus]Outcome
68Mean Ratio [Abhd12]Calculated inhibitor-treated/DMSO ratio for Abhd12 as mean for all unique peptides quantified23Floatratio
69Standard Error [Abhd12]Calculated standard error for mean23Float
70Outcome [Esd]One of Active, Inactive, or Not Tested24S-formylglutathione hydrolase [Mus musculus]Outcome
71Mean Ratio [Esd]Calculated inhibitor-treated/DMSO ratio for Esd as mean for all unique peptides quantified24Floatratio
72Standard Error [Esd]Calculated standard error for mean24Float
73Outcome [Lipe]One of Active, Inactive, or Not Tested25hormone-sensitive lipase isoform 2 [Mus musculus]Outcome
74Mean Ratio [Lipe]Calculated inhibitor-treated/DMSO ratio for Lipe as mean for all unique peptides quantified25Floatratio
75Standard Error [Lipe]Calculated standard error for mean25Float
76Outcome [Fasn]One of Active, Inactive, or Not Tested26fatty acid synthase [Mus musculus]Outcome
77Mean Ratio [Fasn]Calculated inhibitor-treated/DMSO ratio for Fasn as mean for all unique peptides quantified26Floatratio
78Standard Error [Fasn]Calculated standard error for mean26Float
79Outcome [Pme1]One of Active, Inactive, or Not Tested27protein phosphatase methylesterase 1 [Mus musculus]Outcome
80Mean Ratio [Pme1]Calculated inhibitor-treated/DMSO ratio for Pme1 as mean for all unique peptides quantified27Floatratio
81Standard Error [Pme1]Calculated standard error for mean27Float
82Outcome [Parl]One of Active, Inactive, or Not Tested28presenilins-associated rhomboid-like protein, mitochondrial precursor [Mus musculus]Outcome
83Mean Ratio [Parl]Calculated inhibitor-treated/DMSO ratio for Parl as mean for all unique peptides quantified28Floatratio
84Standard Error [Parl]Calculated standard error for mean28Float
85Outcome [Faah]One of Active, Inactive, or Not Tested29fatty acid amide hydrolase [Mus musculus]Outcome
86Mean Ratio [Faah]Calculated inhibitor-treated/DMSO ratio for Faah as mean for all unique peptides quantified29Floatratio
87Standard Error [Faah]Calculated standard error for mean29Float
88Outcome [Iah1]One of Active, Inactive, or Not Tested30isoamyl acetate-hydrolyzing esterase 1 homolog [Mus musculus]Outcome
89Mean Ratio [Iah1]Calculated inhibitor-treated/DMSO ratio for Iah1 as mean for all unique peptides quantified30Floatratio
90Standard Error [Iah1]Calculated standard error for mean30Float
91Outcome [Pafah1b2]One of Active, Inactive, or Not Tested31platelet-activating factor acetylhydrolase IB subunit beta [Mus musculus]Outcome
92Mean Ratio [Pafah1b2]Calculated inhibitor-treated/DMSO ratio for Pafah1b2 as mean for all unique peptides quantified31Floatratio
93Standard Error [Pafah1b2]Calculated standard error for mean31Float
94Outcome [Abhd10]One of Active, Inactive, or Not Tested32abhydrolase domain-containing protein 10, mitochondrial precursor [Mus musculus]Outcome
95Mean Ratio [Abhd10]Calculated inhibitor-treated/DMSO ratio for Abhd10 as mean for all unique peptides quantified32Floatratio
96Standard Error [Abhd10]Calculated standard error for mean32Float
97Outcome [Lypla2]One of Active, Inactive, or Not Tested33acyl-protein thioesterase 2 [Mus musculus]Outcome
98Mean Ratio [Lypla2]Calculated inhibitor-treated/DMSO ratio for Lypla2 as mean for all unique peptides quantified33Floatratio
99Standard Error [Lypla2]Calculated standard error for mean33Float
100Outcome [Prep]One of Active, Inactive, or Not Tested34prolyl endopeptidase [Mus musculus]Outcome
101Mean Ratio [Prep]Calculated inhibitor-treated/DMSO ratio for Prep as mean for all unique peptides quantified34Floatratio
102Standard Error [Prep]Calculated standard error for mean34Float
103Outcome [Prepl]One of Active, Inactive, or Not Tested35prolyl endopeptidase-like isoform a [Mus musculus]Outcome
104Mean Ratio [Prepl]Calculated inhibitor-treated/DMSO ratio for Prepl as mean for all unique peptides quantified35Floatratio
105Standard Error [Prepl]Calculated standard error for mean35Float
106Outcome [Pafah1b3]One of Active, Inactive, or Not Tested36platelet-activating factor acetylhydrolase IB subunit gamma [Mus musculus]Outcome
107Mean Ratio [Pafah1b3]Calculated inhibitor-treated/DMSO ratio for Pafah1b3 as mean for all unique peptides quantified36Floatratio
108Standard Error [Pafah1b3]Calculated standard error for mean36Float
109Outcome [Ddhd1]One of Active, Inactive, or Not Tested37phospholipase DDHD1 isoform 2 [Mus musculus]Outcome
110Mean Ratio [Ddhd1]Calculated inhibitor-treated/DMSO ratio for Ddhd1 as mean for all unique peptides quantified37Floatratio
111Standard Error [Ddhd1]Calculated standard error for mean37Float
112Outcome [Pafah2]One of Active, Inactive, or Not Tested38platelet-activating factor acetylhydrolase 2, cytoplasmic [Mus musculus]Outcome
113Mean Ratio [Pafah2]Calculated inhibitor-treated/DMSO ratio for Pafah2 as mean for all unique peptides quantified38Floatratio
114Standard Error [Pafah2]Calculated standard error for mean38Float
115Outcome [Apeh]One of Active, Inactive, or Not Tested39Acylpeptide hydrolase [Mus musculus]Outcome
116Mean Ratio [Apeh]Calculated inhibitor-treated/DMSO ratio for Apeh as mean for all unique peptides quantified39Floatratio
117Standard Error [Apeh]Calculated standard error for mean39Float
118Outcome [Lypla3]One of Active, Inactive, or Not Tested40group XV phospholipase A2 precursor [Mus musculus]Outcome
119Mean Ratio [Lypla3]Calculated inhibitor-treated/DMSO ratio for Lypla3 as mean for all unique peptides quantified40Floatratio
120Standard Error [Lypla3]Calculated standard error for mean40Float
121Outcome [Abhd4]One of Active, Inactive, or Not Tested41abhydrolase domain-containing protein 4 isoform 1 [Mus musculus]Outcome
122Mean Ratio [Abhd4]Calculated inhibitor-treated/DMSO ratio for Abhd4 as mean for all unique peptides quantified41Floatratio
123Standard Error [Abhd4]Calculated standard error for mean41Float
124Outcome [Dpp9]One of Active, Inactive, or Not Tested42dipeptidyl peptidase 9 [Mus musculus]Outcome
125Mean Ratio [Dpp9]Calculated inhibitor-treated/DMSO ratio for Dpp9 as mean for all unique peptides quantified42Floatratio
126Standard Error [Dpp9]Calculated standard error for mean42Float
127Outcome [Lypla1]One of Active, Inactive, or Not Tested43acyl-protein thioesterase 1 [Mus musculus]Outcome
128Mean Ratio [Lypla1]Calculated inhibitor-treated/DMSO ratio for Lypla1 as mean for all unique peptides quantified43Floatratio
129Standard Error [Lypla1]Calculated standard error for mean43Float
130Outcome [Tpp2]One of Active, Inactive, or Not Tested44Tpp2 protein [Mus musculus]Outcome
131Mean Ratio [Tpp2]Calculated inhibitor-treated/DMSO ratio for Tpp2 as mean for all unique peptides quantified44Floatratio
132Standard Error [Tpp2]Calculated standard error for mean44Float
133Outcome [Abhd6]One of Active, Inactive, or Not Tested45monoacylglycerol lipase ABHD6 [Mus musculus]Outcome
134Mean Ratio [Abhd6]Calculated inhibitor-treated/DMSO ratio for Abhd6 as mean for all unique peptides quantified45Floatratio
135Standard Error [Abhd6]Calculated standard error for mean45Float
136Outcome [Daglb]One of Active, Inactive, or Not Tested46sn1-specific diacylglycerol lipase beta [Mus musculus]Outcome
137Mean Ratio [Daglb]Calculated inhibitor-treated/DMSO ratio for Daglb as mean for all unique peptides quantified46Floatratio
138Standard Error [Daglb]Calculated standard error for mean46Float
Additional Information
Grant Number: 1 R01 DA025285

Classification
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