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BioAssay: AID 504520

Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) inhibition and selectivity

Name: Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) inhibition and selectivity. ..more
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 Tested Compounds
 Tested Compounds
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Active(6)
 
 
Inactive(14)
 
 
 Tested Substances
 Tested Substances
All(20)
 
 
Active(6)
 
 
Inactive(14)
 
 
AID: 504520
Data Source: The Scripps Research Institute Molecular Screening Center (ABHD11_INH_FLUO_GEL_1XINH_SEL)
BioAssay Type: Panel
Depositor Category: NIH Molecular Libraries Probe Production Network, Assay Provider
BioAssay Version:
Deposit Date: 2011-03-21
Hold-until Date: 2011-10-06
Modify Date: 2011-10-06

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 6
Related Experiments
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AIDNameTypeProbeComment
2174Counterscreen for PME1 inhibitors: fluorescence polarization-based primary biochemical high throughput screening assay to identify inhibitors of lysophospholipase 1 (LYPLA1).Screening depositor-specified cross reference: Primary screen (LYPLA1 inhibitors in singlicate)
2177Counterscreen for PME1 inhibitors: fluorescence polarization-based primary biochemical high throughput screening assay to identify inhibitors of lysophospholipase 2 (LYPLA2).Screening depositor-specified cross reference: Primary screen (LYPLA2 inhibitors in singlicate)
2202Summary of probe development efforts to identify inhibitors of lysophospholipase 1 (LYPLA1).Summary2 depositor-specified cross reference: Summary (LYPLA1 inhibitors)
2203Summary of probe development efforts to identify inhibitors of lysophospholipase 2 (LYPLA2).Summary1 depositor-specified cross reference: Summary (LYPLA2 inhibitors)
2232Counterscreen for PME1 inhibitors: fluorescence polarization-based biochemical high throughput confirmation assay to identify inhibitors of lysophospholipase 2 (LYPLA2).Screening depositor-specified cross reference: Confirmation screen (LYPLA2 inhibitors in triplicate)
2233Counterscreen for PME1 inhibitors: fluorescence polarization-based biochemical high throughput confirmation assay for inhibitors of lysophospholipase 1 (LYPLA1).Screening depositor-specified cross reference: Confirmation screen (LYPLA1 inhibitors in triplicate)
493105Assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibition of recombinant and endogenous enzymeOther depositor-specified cross reference: Confirmation screen (LYPLA1 and LYPLA2 inhibitors in singlicate)
493108Late stage assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: fluorescence-based cell-based inhibitionOther depositor-specified cross reference: Late stage screen (LYPLA1 and LYPLA2 inhibitors in singlicate)
493109Late stage assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: LC-MS/MS assay to assess binding of compounds to active siteOther depositor-specified cross reference: Late stage LCMS assay (LYPLA1)
493110Late stage assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: Gel-based Activity-Based Protein Profiling (ABPP) IC50 for LYPLA1 and LYPLA2Confirmatory depositor-specified cross reference: Late stage dose response (LYPLA1 and LYPLA2 inhibitors in triplicate)
493111Late stage assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibition and selectivityOther depositor-specified cross reference: Late stage screen (LYPLA1 and LYPLA2 inhibitors in singlicate)
493154Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Gel-based Activity-Based Protein Profiling (ABPP) IC50 for off-target ABHD11Confirmatory depositor-specified cross reference: Late stage dose response counterscreen (ABHD11 inhibitors in triplicate)
493161Late stage assay provider results from the probe development effort to identify dual inhibitors of LYPLA1 and LYPLA2: absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compoundsConfirmatory depositor-specified cross reference: Late stage dose response counterscreen (T-cell cytotoxicity in quadruplicate)
504892Late stage assay provider results from the probe development effort to identify inhibitors of ABHD11: Fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) inhibition of the human isoform of ABHD11Other depositor-specified cross reference
651978Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: LCMS-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis in vitroOther depositor-specified cross reference
651979Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis in situOther depositor-specified cross reference
651980Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis in situOther depositor-specified cross reference
651981Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: LCMS-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis in vitroOther depositor-specified cross reference
651985Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP evaluation of activity in vivoOther depositor-specified cross reference
651986Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP evaluation of activity in situOther depositor-specified cross reference
651987Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP gel filtration assay to assess binding modeOther depositor-specified cross reference
651988Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibition and selectivityOther depositor-specified cross reference
651990Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical dose-response gel-based ABPPConfirmatory depositor-specified cross reference
651991Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1 and LYPLA2: Absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compoundsConfirmatory depositor-specified cross reference
651998Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: Substrate-based fluorescence-based biochemical determination of kinetic parametersConfirmatory depositor-specified cross reference
652001Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Substrate-based fluorescence-based biochemical determination of kinetic parametersConfirmatory depositor-specified cross reference
652003Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: fluorescence-based biochemical dose-response assayConfirmatory depositor-specified cross reference
652004Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: fluorescence-based biochemical dose-response assayConfirmatory depositor-specified cross reference
652018Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: LCMS-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysis in vitro, Set 2Other depositor-specified cross reference
652029Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibitionOther depositor-specified cross reference
652030Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibition and selectivityOther depositor-specified cross reference
743117Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP inhibition potency and selectivityOther depositor-specified cross reference
743118Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical dose-response gel-based ABPP in vitroConfirmatory depositor-specified cross reference
743119Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical dose-response gel-based ABPP in situConfirmatory depositor-specified cross reference
743127Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compoundsConfirmatory depositor-specified cross reference
743132Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical dose-response gel-based ABPP in vitro in mouse brainConfirmatory depositor-specified cross reference
743133Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP gel filtration assay to assess inhibitor binding modeOther depositor-specified cross reference
743134Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: Fluorescence-based biochemical gel-based ABPP assay to assess in vivo activityOther depositor-specified cross reference
743137Late stage assay provider results from the extended probe development effort to identify inhibitors of LYPLA1 and LYPLA2: LCMS-based cell-based Activity-Based Protein Profiling (ABPP) SILAC selectivity analysisOther depositor-specified cross reference
2143Summary of probe development efforts to identify inhibitors of Protein Phosphatase Methylesterase 1 (PME-1).Summary3 same project related to Summary assay
504482Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based cell-based gel-based Activity-Based Protein Profiling (ABPP) IC50 for anti-target ABHD11Confirmatory same project related to Summary assay
504498Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: LC-MS/MS assay to assess binding of compounds to active site of anti-target ABHD11Other same project related to Summary assay
504505Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based cell-based gel-based Activity-Based Protein Profiling (ABPP) percent inhibition for anti-target ABHD11Other same project related to Summary assay
504507Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) IC50 for anti-target ABHD11 Set 2Confirmatory same project related to Summary assay
504510Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compounds set 2Confirmatory same project related to Summary assay
504522Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: LC-MS-based cell-based SILAC Activity-Based Protein Profiling (ABPP) for anti-target ABHD11Other same project related to Summary assay
2143Summary of probe development efforts to identify inhibitors of Protein Phosphatase Methylesterase 1 (PME-1).Summary3 same project related to Summary assay
504482Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based cell-based gel-based Activity-Based Protein Profiling (ABPP) IC50 for anti-target ABHD11Confirmatory same project related to Summary assay
504498Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: LC-MS/MS assay to assess binding of compounds to active site of anti-target ABHD11Other same project related to Summary assay
504505Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based cell-based gel-based Activity-Based Protein Profiling (ABPP) percent inhibition for anti-target ABHD11Other same project related to Summary assay
504507Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) IC50 for anti-target ABHD11 Set 2Confirmatory same project related to Summary assay
504510Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: absorbance-based cell-based dose response assay to determine cytotoxicity of inhibitor compounds set 2Confirmatory same project related to Summary assay
504522Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: LC-MS-based cell-based SILAC Activity-Based Protein Profiling (ABPP) for anti-target ABHD11Other 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 Provider: Benjamin Cravatt, TSRI
Network: Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R01 CA132630
Grant Proposal PI: Benjamin Cravatt, TSRI
External Assay ID: ABHD11_INH_FLUO_GEL_1XINH_SEL

Name: Late stage assay provider results from the probe development effort to identify inhibitors of LYPLA1: fluorescence-based biochemical gel-based Activity-Based Protein Profiling (ABPP) inhibition and selectivity.

Description:

Protein palmitoylation is an essential post-translational modification necessary for trafficking and localization of regulatory proteins that play key roles in cell growth and signaling. Numerous proteins have been identified as targets of palmitoylation, including cytoskeletal proteins, kinases, receptors, and other proteins involved in various aspects of cellular signaling and homeostasis (1). Using a global chemo-proteomic method for the metabolic incorporation and identification of palmitoylated proteins, we were able to identify hundreds of palmitoylated proteins, revealing palmitoylation as a widespread post-translational modification (PTM) (2). Palmitoylation involves an acyl-thioester linkage to specific cysteines (3,4). Given the labile properties of thioesters, palmitoylation is potentially reversible and may be regulated in a manner analogous to other PTMs (e.g., phosphorylation). As such, identification of proteins responsible for the dynamic modulation of palmitoylation is paramount to understanding its patho/physiological roles. For example, multiple oncogenes, including HRAS and SRC, require palmitoylation for malignant transformation (5), suggesting protein palmitoyl thioesterases may have tumor suppressor activity required to repress aberrant growth signaling. More than a decade ago, the cytosolic serine hydrolase acyl-protein thioesterase 1 (APT1) was identified as an in vitro HRAS palmitoyl thioesterase (6). Initially classified as lysophospholipase 1 (LYPLA1) (7), the enzyme has since been demonstrated to have several hundred-fold higher activity as a protein thioesterase. While the in vitro data (6,8) provided an intriguing clue to its possible role in vivo, prior to our studies, little was known about the in vivo thioesterase activity of LYPLA1. Upon retroviral shRNA knockdown of LYPLA1, we found that HRAS was robustly hyper-palmitoylated, providing the first evidence that the endogenous enzyme is a functional protein palmitoyl thioesterase capable of regulating HRAS palmitoylation in mammalian cells. However, shRNA resulted in only an 80% reduction in LYPLA1 expression (unpublished). LYPLA2 (a.k.a. APT2) is 65% identical to LYPLA1, and also exhibits lysophospholipase activity in vitro, but its potential role as a thioesterase is unknown (9). shRNA knockdown studies of LYPLA2 revealed only partial knockdown of the enzyme, making substrate identification inconclusive (unpublished). A principle goal of post-genomic research is the determination of the molecular and cellular role of uncharacterized enzymes like LYPLA1 and LYPLA2. As such, a dual inhibitor selective for both LYPLA1 and LYPLA2 would greatly aid investigations into the biological function of these related enzymes. Several inhibitors of LYPLA1 have been described (10,11), but none of these agents have proven capable of inhibiting LYPLA1 activity in cells, and no selective inhibitors of LYPLA2 have been reported to date. To comprehensively identify LYPLA1 and LYPLA2 substrates and functionally test the role of these enzymes in dynamic de-palmitoylation and tumorigenesis, development of a high affinity inhibitor, capable of achieving temporal and more complete control over activity, is critical. Alpha/beta hydrolase domain-containing protein 11 (ABHD11) is a poorly characterized serine hydrolase; all that is known about its biology is that it is a mitochondrial enzyme (12) with broad tissue distribution, has little sequence homology to other proteins, and its gene is located in a region of chromosome 7 that is hemizygously deleted in Williams-Beuren syndrome, a rare genetic disease with symptoms that include vascular stenosis, mental retardation, and excessive sociability (13).

References:

1. Smotrys, J.E. and Linder, M.E. PALMITOYLATION OF INTRACELLULAR SIGNALING PROTEINS: Regulation and Function. Annual Review of Biochemistry, 2004. 73: 559-587.
2. Martin, B.R. and Cravatt, B.F. Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods, 2009. 6: 135-138.
3. Magee, A.I., Koyama, A.H., Malfer, C., Wen, D. and Schlesinger, M. J. Release of fatty acids from virus glycoproteins by hydroxylamine. Biochimica et Biophysica Acta (BBA) - General Subjects, 1984. 798: 156-166.
4. Rose, J.K., Adams, G.A. and Gallione, C.J. The presence of cysteine in the cytoplasmic domain of the vesicular stomatitis virus glycoprotein is required for palmitate addition. Proc Natl Acad Sci USA, 1984. 81: 2050-2054.
5. Willumsen, B.M., Cox, A.D., Solski, P.A., Der, C.J. and Buss, J.E. Novel determinants of H-Ras plasma membrane localization and transformation. Oncogene, 1996. 13: 1901-1909.
6. Duncan, J.A. and Gilman, A.G. A Cytoplasmic Acyl-Protein Thioesterase That Removes Palmitate from G Protein alpha Subunits and p21RAS. J Biol Chem, 1998. 273: 15830-15837.
7. Sugimoto, H., Hayashi, H. & Yamashita, S. Purification, cDNA cloning, and regulation of lysophospholipase from rat liver. J Biol Chem, 1996. 271: 7705-7711.
8. Hirano, T. et al. Thioesterase activity and subcellular localization of acylprotein thioesterase 1/lysophospholipase 1. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2009. 1791: 797-805.
9. Toyoda, T., Sugimoto, H. and Yamashita, S. Sequence, expression in Escherichia coli, and characterization of lysophospholipase II. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1999. 1437: 182-193.
10. Biel, M., Deck, P., Giannis, A. and Waldmann, H. Synthesis and Evaluation of Acyl Protein Thioesterase 1 (APT1) Inhibitors. Chemistry - A European Journal, 2006. 12: 4121-4143.
11. Deck, P. et al. Development and Biological Evaluation of Acyl Protein Thioesterase 1 (APT1) Inhibitors. Angewandte Chemie International Edition, 2005. 44: 4975-4980.
12. Forner, F., et al., Quantitative proteomic comparison of rat mitochondria from muscle, heart, and liver. Mol. Cell. Proteomics, 2006. 5(4): p. 608-19.
13. Schubert, C., The genomic basis of the Williams-Beuren syndrome. Cell. Mol. Life Sci., 2009. 66(7): p. 1178-97.

Keywords:

late stage, late stage AID, assay provider, powders, LYPLA1, lysophospholipase 1, LYPLA2, lysophospholipase 2, APT1, acyl-protein thioesterase 1, APT2, acyl-protein thioesterase 2, palmitoylation, alpha/beta hydrolase domain-containing protein 11, abhydrolase domain-containing protein 11, ABHD11, oncogene, tumor suppressor, serine hydrolase, counterscreen, inhibitor, selectivity, anti-targets, activity-based protein profiling, ABPP, gel-based ABPP, fluorophosphonate rhodamine, FP-Rh, BW5147, murine T cells, T cells, 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
1ABHD11137Abhydrolase domain containing 11 [Mus musculus] [gi:47682716]
Taxonomy id: 10090
Gene id: 68758
2PAFAH2218platelet-activating factor acetylhydrolase 2, cytoplasmic [Mus musculus] [gi:225579137]
Taxonomy id: 10090
Gene id: 100163
3LYPLA1614Lypla1 [Mus musculus] [gi:71059731]
Taxonomy id: 10090
Gene id: 18777
4LYPLA220lysophospholipase 2 [Mus musculus] [gi:123122209]
Taxonomy id: 10090
Gene id: 26394
5ESD20Esterase D/formylglutathione hydrolase [Mus musculus] [gi:55777188]
Taxonomy id: 10090
Gene id: 13885

§ Panel component ID.
Protocol
Assay Overview:
The purpose of this assay is to determine whether powder samples of test compounds can inhibit LYPLA1 and LYPLA2 in a complex proteomic lysate and to estimate compound selectivity in an activity-based proteomic profiling (ABPP) assay. In this assay, a complex proteome is incubated with test compound 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 LYPLA1 and/or LYPLA2 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:
Soluble proteome (1 mg/ml in DPBS) of BW5147-derived murine T cells was treated with 30 nM, 200 nM, or 1.5 uM test compound (1 uL of a 50x stock in DMSO). Test compounds were incubated for 30 minutes at 25 C (50 uL reaction volume). FP-Rh (1 uL of 50x stock in DMSO) was added to a final concentration of 2 uM. The reaction was incubated for 30 minutes at 25 C, quenched with 2x SDS-PAGE loading buffer, 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 target (alpha/beta hydrolase domain-containing protein 11 [ABHD11]) and anti-target (lysophospholipase 1 [LYPLA1], lysophospholipase 2 [LYPLA1], platelet-activating factor acetylhydrolase 2 [PAFAH2], and esterase D/formylglutathione hydrolase [ESD]) 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 treated with test compound.
High_Control is defined as target or anti-target 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 ABHD11 is observed.
If [Conc_<50%_INH_Anti-target] is equal to [Conc_>=50%_INH_target], then Fold Selectivity is > 1, unless [Conc_>=50%_INH_target] is the highest concentration tested. 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 0.15 uM were considered active. Compounds with less than 50% inhibition at 0.15 uM were considered inactive.
The reported PubChem Activity Score has been normalized to 100% of the observed value at 0.15 uM.
ABHD11 Score: The PubChem Activity Score range for active compounds is 100-50, and for inactive compounds 0-0.
PAFAH2 Score: The PubChem Activity Score range for active compounds is 100-100, and for inactive compounds 0-0.
LYPLA1 Score: The PubChem Activity Score range for active compounds is 100-50, and for inactive compounds 0-0.
LYPLA2 Score: The PubChem Activity Score range for inactive compounds is 0-0. There are no active compounds.
LYPLA2 Score: The PubChem Activity Score range for inactive compounds is 100-0. There are no active compounds.
Overall Outcome and Score:
Compounds that were active for inhibition of ABHD11 and inactive for inhibition of all anti-targets (PAFAH2, LYPLA1, LYPLA2, or ESD) were assigned a PubChem Activity Outcome of active. Compounds that were inactive for ABHD11 were assigned a PubChem Activity Outcome of inactive. Compounds that were active for inhibition of ABHD11 and active for inhibition of one or more anti-targets (PAFAH2, LYPLA1, LYPLA2, and ESD) were assigned a PubChem Activity Outcome of inactive.
Active compounds were given a score of 100, and inactive compounds were given a score of 0.
The PubChem Activity Score range for active compounds is 100-100, and for inactive compounds 0-0.
List of Reagents:
Soluble proteome of BW5147-derived murine T-cells
FP-Rh (provided by the Assay Provider)
DPBS (Cellgro 20-031-CV)
Comment
This assay was performed by the assay provider with powder samples of synthetic compounds.
Categorized Comment - additional comments and annotations
From PubChem:
Assay Format: Biochemical
Result Definitions
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TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Outcome [ABHD11]One of Active, Inactive, or Not Tested for inhibition of ABHD111Abhydrolase domain containing 11 [Mus musculus]Outcome
2Score [ABHD11]The BioAssay activity ranking score1Integer
3Inhibition at 0.03 uM [ABHD11] (0.03μM**)Inhibition of ABHD11 in murine Tcell soluble proteome upon 0.03 uM compound treatment as assessed by competitive ABPP.1Integer%
4Inhibition at 0.15 uM [ABHD11] (0.15μM**)Inhibition of ABHD11 in murine T cell soluble proteome upon 0.15 uM compound treatment as assessed by competitive ABPP.1Integer%
5Inhibition at 0.75 uM [ABHD11] (0.75μM**)Inhibition of ABHD11 in murine T cell soluble proteome upon 0.75 uM compound treatment as assessed by competitive ABPP.1Integer%
6Outcome [PAFAH2]One of Active, Inactive, or Not Tested for inhibition of PAFAH22platelet-activating factor acetylhydrolase 2, cytoplasmic [Mus musculus]Outcome
7Score [PAFAH2]The BioAssay activity ranking score2Integer
8Inhibition at 0.03 uM [PAFAH2] (0.03μM**)Inhibition of PAFAH2in murine Tcell soluble proteome upon 0.03 uM compound treatment as assessed by competitive ABPP.2Integer%
9Inhibition at 0.15 uM [PAFAH2] (0.15μM**)Inhibition of PAFAH2 in murine T cell soluble proteome upon 0.15 uM compound treatment as assessed by competitive ABPP.2Integer%
10Inhibition at 0.75 uM [PAFAH2] (0.75μM**)Inhibition of PAFAH2 in murine T cell soluble proteome upon 0.75 uM compound treatment as assessed by competitive ABPP.2Integer%
11Qualifier [Fold Selectivity, PAFAH2]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.2String
12Fold Selectivity [PAFAH2]The ratio of the test compound concentration at which less than or equal to 50% inhibition of the anti-target PAFAH2 is observed over the test compound concentration at which greater than or equal to 50% inhibition of ABHD11 is observed.2Integerratio
13Outcome [LYPLA1]One of Active, Inactive, or Not Tested for inhibition of LYPLA13Lypla1 [Mus musculus]Outcome
14Score [LYPLA1]The BioAssay activity ranking score3Integer
15Inhibition at 0.03 uM [LYPLA1] (0.03μM**)Inhibition of LYPLA1 in murine Tcell soluble proteome upon 0.03 uM compound treatment as assessed by competitive ABPP.3Integer%
16Inhibition at 0.15 uM [LYPLA1] (0.15μM**)Inhibition of LYPLA1 in murine T cell soluble proteome upon 0.15 uM compound treatment as assessed by competitive ABPP.3Integer%
17Inhibition at 0.75 uM [LYPLA1] (0.75μM**)Inhibition of LYPLA1 in murine T cell soluble proteome upon 0.75 uM compound treatment as assessed by competitive ABPP.3Integer%
18Qualifier [Fold Selectivity, LYPLA1]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.3String
19Fold Selectivity [LYPLA1]The ratio of the test compound concentration at which less than or equal to 50% inhibition of the anti-target LYPLA1 is observed over the test compound concentration at which greater than or equal to 50% inhibition of ABHD11 is observed.3Integerratio
20Outcome [LYPLA2]One of Active, Inactive, or Not Tested for inhibition of LYPLA24lysophospholipase 2 [Mus musculus]Outcome
21Score [LYPLA2]The BioAssay activity ranking score4Integer
22Inhibition at 0.03 uM [LYPLA2] (0.03μM**)Inhibition of LYPLA2 in murine Tcell soluble proteome upon 0.03 uM compound treatment as assessed by competitive ABPP.4Integer%
23Inhibition at 0.15 uM [LYPLA2] (0.15μM**)Inhibition of LYPLA2 in murine T cell soluble proteome upon 0.15 uM compound treatment as assessed by competitive ABPP.4Integer%
24Inhibition at 0.75 uM [LYPLA2] (0.75μM**)Inhibition of LYPLA2 in murine T cell soluble proteome upon 0.75 uM compound treatment as assessed by competitive ABPP.4Integer%
25Qualifier [Fold Selectivity, LYPLA2]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.4String
26Fold Selectivity [LYPLA2]The ratio of the test compound concentration at which less than or equal to 50% inhibition of the anti-target LYPLA2 is observed over the test compound concentration at which greater than or equal to 50% inhibition of ABHD11 is observed.4Integerratio
27Outcome [ESD]One of Active, Inactive, or Not Tested for inhibition of ESD5Esterase D/formylglutathione hydrolase [Mus musculus]Outcome
28Score [ESD]The BioAssay activity ranking score5Integer
29Inhibition at 0.03 uM [ESD] (0.03μM**)Inhibition of ESD in murine Tcell soluble proteome upon 0.03 uM compound treatment as assessed by competitive ABPP.5Integer%
30Inhibition at 0.15 uM [ESD] (0.15μM**)Inhibition of ESD in murine T cell soluble proteome upon 0.15 uM compound treatment as assessed by competitive ABPP.5Integer%
31Inhibition at 0.75 uM [ESD] (0.75μM**)Inhibition of ESD in murine T cell soluble proteome upon 0.75 uM compound treatment as assessed by competitive ABPP.5Integer%
32Qualifier [Fold Selectivity, ESD]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity.5String
33Fold Selectivity [ESD]The ratio of the test compound concentration at which less than or equal to 50% inhibition of the anti-target ESD is observed over the test compound concentration at which greater than or equal to 50% inhibition of ABHD11 is observed.5Integerratio
34Summary: Anti-targets at 0.03 uMName(s) of Anti-targets with greater than or equal to 50% inhibition at 0.03 uM compound treatment as assessed by competitive ABPPString
35Summary: Anti-targets at 0.15 uMName(s) of Anti-targets with greater than or equal to 50% inhibition at 0.15 uM compound treatment as assessed by competitive ABPPString
36Summary: Anti-targets at 0.75 uMName(s) of Anti-targets with greater than or equal to 50% inhibition at 0.75 uM compound treatment as assessed by competitive ABPPString
37Qualifier [Summary: Fold Selectivity]Qualifier identifies if the resultant fold selectivity was determined manually to be less than or greater than its listed fold selectivity. String
38Summary: Fold SelectivityThe smallest fold selectivity ratio of the test compound concentration at which less than or equal to 50% inhibition of any anti-target is observed over the test compound concentration at which greater than or equal to 50% inhibition of ABDH11 is observed.Integerratio

** Test Concentration. § Panel component ID.
Additional Information
Grant Number: 1 R01 CA132630

Classification
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