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BioAssay: AID 652001

Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Substrate-based fluorescence-based biochemical determination of kinetic parameters

Name: Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Substrate-based fluorescence-based biochemical determination of kinetic parameters. ..more
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 Tested Compounds
 Tested Compounds
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Active(1)
 
 
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Active(1)
 
 
AID: 652001
Data Source: The Scripps Research Institute Molecular Screening Center (LYPLA2_INH_FLUO_SUBSTRATE_4XKINETICS)
BioAssay Type: Panel, Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network, Assay Provider
BioAssay Version:
Deposit Date: 2013-01-30
Hold-until Date: 2013-10-18
Modify Date: 2013-10-18

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: 1
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)
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 depositor-specified cross reference: Late stage dose repsonse (ABHD11 inhibitors in triplicate)
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 depositor-specified cross reference: Late stage MOA assay (ABDH11 LCMS)
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 depositor-specified cross reference: Late stage screen (ABHD11 inhibitors in singlicate, in situ)
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 depositor-specified cross reference: Late stage dose response (ABHD11 inhibitors in triplicate)
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 depositor-specified cross reference: Late stage dose repsonse counterscreen (T-cell cytotoxicity in quadruplicate)
504520Late 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 selectivityOther depositor-specified cross reference: Late stage screen (LYPLA1 and LYPLA2 inhibitors in singlicate)
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 depositor-specified cross reference: Late stage panel screen (ABHD11 SILAC ratio)
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: Late stage counterscreen (ABHD11 inhibitors in singlicate)
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: Late stage assay (SILAC selectivity analysis in vitro)
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: Late stage assay (SILAC selectivity analysis in situ)
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: Late stage assay (SILAC selectivity analysis in situ)
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: Late stage assay (SILAC selectivity analysis in vitro)
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: Late stage assay (LYPLA1 and LYPLA2 inhibitors activity in vivo)
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: Late stage assay (LYPLA1 and LYPLA2 inhibitors activity in situ)
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: Late stage assay (binding mode)
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
743137 On Hold
2143Summary of probe development efforts to identify inhibitors of Protein Phosphatase Methylesterase 1 (PME-1).Summary3 same project related to Summary assay
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 same project related to Summary assay
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 same project related to Summary assay
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 same project related to Summary assay
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 same project related to Summary assay
652003Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: fluorescence-based biochemical dose-response assayConfirmatory same project related to Summary assay
652004Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: fluorescence-based biochemical dose-response assayConfirmatory 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
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 same project related to Summary assay
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 same project related to Summary assay
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 same project related to Summary assay
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 same project related to Summary assay
652003Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA1: fluorescence-based biochemical dose-response assayConfirmatory same project related to Summary assay
652004Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: fluorescence-based biochemical dose-response assayConfirmatory 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: LYPLA2_INH_FLUO_SUBSTRATE_4XKINETICS

Name: Late stage assay provider results from the probe development effort to identify selective inhibitors of LYPLA2: Substrate-based fluorescence-based biochemical determination of kinetic parameters.

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, selective inhibitors of LYPLA1 or LYPLA2 would greatly aid investigations into the biological function of these 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 high affinity inhibitors, capable of achieving temporal and more complete control over activity, is critical.

References:

1. Dekker, F.J., et al., Small-molecule inhibition of APT1 affects Ras localization and signaling. Nat. Chem. Biol., 2010. 6(6): p. 449-56.
2. Duncan, J.A. and A.G. Gilman, A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J. Biol. Chem., 1998. 273(25): p. 15830-7.
3. Sugimoto, H., H. Hayashi, and S. Yamashita, Purification, cDNA cloning, and regulation of lysophospholipase from rat liver. J. Biol. Chem., 1996. 271(13): p. 7705-11.
4. Toyoda, T., H. Sugimoto, and S. Yamashita, Sequence, expression in Escherichia coli, and characterization of lysophospholipase II. Biochim. Biophys. Acta, 1999. 1437(2): p. 182-93.
5. Biel, M., et al., Synthesis and evaluation of acyl protein thioesterase 1 (APT1) inhibitors. Chemistry, 2006. 12(15): p. 4121-43.
6. Deck, P., et al., Development and biological evaluation of acyl protein thioesterase 1 (APT1) inhibitors. Angew. Chem. Int. Ed. Engl., 2005. 44(31): p. 4975-80.
7. Jessani, N., et al., Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proc. Natl. Acad. Sci. U. S. A., 2002. 99(16): p. 10335-40.
8. Leung, D., et al., Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. Nat. Biotechnol., 2003. 21(6): p. 687-91.
9. Bachovchin, D.A., et al., Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes. Nat. Biotechnol., 2009. 27(4): p. 387-94.
10. Forner, F., et al., Quantitative proteomic comparison of rat mitochondria from muscle, heart, and liver. Mol. Cell. Proteomics, 2006. 5(4): p. 608-19.
11. 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, LYPLA2, lysophospholipase 2, APT2, acyl-protein thioesterase 2, serine hydrolase, palmitoylation, protein palmitoylation, counterscreen, inhibitor, inhibition, substrate, resorufin acetate, kinetic, kinetic parameter, Michealis-Menten, Michealis-Menten kinetics, Cheng-Prusoff, Cheng-Prusoff equation, Vmax, Km, Ki, IC50, dose response, fluorescence, fluorescence intensity, Scripps, Scripps Research Institute Molecular Screening Center, SRIMSC, Molecular Libraries Probe Production Centers Network, MLPCN
Panel Information
Assays
PID§NameSubstancePanel TargetsDescriptionAdditional Information
ActiveInactive
1LYPLA2acyl-protein thioesterase 2 [Homo sapiens] [gi:9966764]
Taxonomy id: 9606
Gene id: 11313
2LYPLA2 (no test compound)acyl-protein thioesterase 2 [Homo sapiens] [gi:9966764]
Taxonomy id: 9606
Gene id: 11313

§ Panel component ID.
Protocol
Assay Overview:
The purpose of this assay is to determine kinetic parameters Vmax and Km for LYPLA2, and kinetic parameters Ki and IC50 values for powder samples of test compounds that act as reversible inhibitors for LYPLA2 using a fluorogenic substrate (resorufin acetate)-based assay. To determine Vmax and Km values, LYPLA2 is incubated with varying concentrations of substrate and the rate of enzymatic hydrolysis (as indicated by fluorescence intensity) is monitored as a function of time. Initial velocities for each substrate concentration are determined and used to calculate Vmax and Km using standard Michaelis-Menten kinetics. To obtain IC50 values, LYPLA2 is incubated with varying concentrations of inhibitor at a fixed substrate concentration, and fluorescence intensity is monitored as a function of time. Initial velocities determined for each inhibitor concentration are used to calculate IC50 values. From these data, Ki values can be calculated using the Cheng-Prusoff equation. For all assays, enzyme activity is calculated relative to a catalytically-dead (LYPLA2-S112A) enzyme control.
Protocol Summary:
Substrate resorufin acetate was dissolved in DMSO. Active or catalytically-dead LYPLA1 enzyme solutions (10 nM) were prepared in DPBS adjusted to pH 6.5 with sodium acetate and 0.2% pluronic F127. In a black-bottom half-area 96 well plate, 5 uL of substrate was aliquoted at varying concentrations. The assay was initiated upon addition of enzyme (95 uL of 10 nM) using a multi-channel pipette, and reactions quickly mixed by pipetting up and down several times. Fluorescence intensity was measured on a Tecan F500 plate reader at room temperature every 30 seconds using a 525/35 nM excitation filter, a 600/10 nM emission filter, and a 560 LP dichroic filter. Each concentration was performed as 4 separate replicates for both the active and dead enzymes. After subtracting background (average fluorescence intensity of catalytically-dead enzyme at each time point for each assay condition), fluorescence intensity was plotted vs. time and initial velocities were calculated using standard straight-line plots (with non-linear regression) in GraphPad Prism using the first ~6 minutes of the reaction. The initial velocities (+/- SEM, plotted vs. substrate concentration) were analyzed using standard Michaelis-Menten kinetics (GraphPad Prism) to derive the Vmax and Km values. Software-generated values and SEM are reported.
To calculate the Ki values, the same experimental setup was used. Active or catalytically-dead LYPLA2-S122A enzyme (10 nM) was incubated with varying inhibitor concentrations (11-point series from 10 uM to 0.05 uM, and 0 uM) for 15 minutes (95 uL total volume), and then aliquoted into 96-well plate wells containing a fixed concentration of resorufin acetate substrate (50 uM, 5 uL). Fluorescence intensity was monitored as described above. After background subtraction, the initial velocities were calculated as described above, plotted vs. inhibitor concentration, and analyzed to derive IC50 values (standard one phase decay, GraphPad Prism). Software-generated values and SEM are reported. The Ki values were calculated using the Cheng-Prusoff equation:
Ki = ( IC50 ) / ( 1 + [S] / Km )
Where:
IC50 = IC50
[S] = substrate concentration
Km = Michaelis constant
PubChem Activity Outcome and Score:
Compounds with an IC50 value of less than or equal to 10 uM were considered active. Compounds with an IC50 value of greater than 10 uM were considered inactive.
Activity score was then ranked by the potency, with the most potent compounds assigned the highest activity scores.
The PubChem Activity Score range for active compounds is 100-100. There are no inactive compounds.
List of Reagents:
Resorufin acetate (SigmaAldrich, 83636)
Recombinant human LYPLA1 (provided by the Assay Provider)
Catalytically-dead (S122A) recombinant human LYPLA2 (provided by the Assay Provider)
DPBS (Cellgro 20-031-CV)
Sodium acetate (FisherScientific, BP333)
Pluronic F127 (Invitrogen, P6866)
Comment
This assay was performed by the assay provider with powder samples of synthetic compounds.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay: CurveFit [1]: Equation: = ( [Y0] - [Plateau] ) * exp( -[Rate Constant] * [Concentration] ) + [Plateau]
Assay: CurveFit [2]: Equation: = [Vmax] * [Substrate Concentration] / ( [Km] + [Substrate Concentration] )
Assay: Dictionary: Version: 0.1
From PubChem:
Assay Format: Biochemical
Result Definitions
Show more
TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Average IC50 [LYPLA2]*The average concentration at which 50 percent inhibiton is observed; (IC50), calculated from the initial reaction velocity as described in the txst; shown in micromolar.1acyl-protein thioesterase 2 [Homo sapiens]FloatμM
2Standard Error of IC50 [LYPLA2]Standard error of the mean for the IC50 value.1Float
3Average Ki [LYPLA2]The value of the inhibition constant (Ki), calculated from the IC50 as described in the text; shown in micromolar.1FloatμM
4Standard Error of Ki [LYPLA2]Standard error of the mean for the Ki value.1Float
5Y0 [LYPLA2]Y0 is the initial velocity when concentration is zero.1Float
6Plateau [LYPLA2]Plateau is the initial velocity value at infinite concentration.1Float
7Rate Constant [LYPLA2]Is the rate constant of the equation. Expressed in inverse uM.1Float
8Span [LYPLA2]Span is the difference between Y0 and Plateau.1Float
9Average Initial Velocity at 0.05 uM [LYPLA2] (0.05μM**)Normalized average initial velocity at 0.05 uM compound concentration.1Floatratio
10Standard Error of Initial Velocity at 0.05 uM [LYPLA2]Standard Error of average initial velocity at 0.05 uM compound concentration.1Float
11Average Initial Velocity at 0.1 uM [LYPLA2] (0.1μM**)Normalized average initial velocity at 0.1 uM compound concentration.1Floatratio
12Standard Error of Initial Velocity at 0.1 uM [LYPLA2]Standard Error of average initial velocity at 0.1 uM compound concentration.1Float
13Average Initial Velocity at 0.2 uM [LYPLA2] (0.2μM**)Normalized average initial velocity at 0.2 uM compound concentration.1Floatratio
14Standard Error of Initial Velocity at 0.2 uM [LYPLA2]Standard Error of average initial velocity at 0.2 uM compound concentration.1Float
15Average Initial Velocity at 0.4 uM [LYPLA2] (0.4μM**)Normalized average initial velocity at 0.4 uM compound concentration.1Floatratio
16Standard Error of Initial Velocity at 0.4 uM [LYPLA2]Standard Error of average initial velocity at 0.4 uM compound concentration.1Float
17Average Initial Velocity at 0.6 uM [LYPLA2] (0.6μM**)Normalized average initial velocity at 0.6 uM compound concentration.1Floatratio
18Standard Error of Initial Velocity at 0.6 uM [LYPLA2]Standard Error of average initial velocity at 0.6 uM compound concentration.1Float
19Average Initial Velocity at 0.8 uM [LYPLA2] (0.8μM**)Normalized average initial velocity at 0.8 uM compound concentration.1Floatratio
20Standard Error of Initial Velocity at 0.8 uM [LYPLA2]Standard Error of average initial velocity at 0.8 uM compound concentration.1Float
21Average Initial Velocity at 1 uM [LYPLA2] (1μM**)Normalized average initial velocity at 1 uM compound concentration.1Floatratio
22Standard Error of Initial Velocity at 1 uM [LYPLA2]Standard Error of average initial velocity at 1 uM compound concentration.1Float
23Average Initial Velocity at 2 uM [LYPLA2] (2μM**)Normalized average initial velocity at 2 uM compound concentration.1Floatratio
24Standard Error of Initial Velocity at 2 uM [LYPLA2]Standard Error of average initial velocity at 2 uM compound concentration.1Float
25Average Initial Velocity at 3 uM [LYPLA2] (3μM**)Normalized average initial velocity at 3 uM compound concentration.1Floatratio
26Standard Error of Initial Velocity at 3 uM [LYPLA2]Standard Error of average initial velocity at 3 uM compound concentration.1Float
27Average Initial Velocity at 6 uM [LYPLA2] (6μM**)Normalized average initial velocity at 6 uM compound concentration.1Floatratio
28Standard Error of Initial Velocity at 6 uM [LYPLA2]Standard Error of average initial velocity at 6 uM compound concentration.1Float
29Average Initial Velocity at 10 uM [LYPLA2] (10μM**)Normalized average initial velocity at 10 uM compound concentration.1Floatratio
30Standard Error of Initial Velocity at 10 uM [LYPLA2]Standard Error of average initial velocity at 10 uM compound concentration.1Float
31Average Vmax [LYPLA2 (no test compound]The valuie of the enzyme's maximum rate (Vmax), calculated from the initial reaction velocity as described in the text, expressed in nanomolar2acyl-protein thioesterase 2 [Homo sapiens]FloatnM
32Standard Error of Vmax [LYPLA2 (no test compound)]Standard error of the mean for the Vmax value.2Float
33Average Km [LYPLA2 (no test compound)]The value of the Michaelis constant (Km) calculated from the initial reaction velocity as described in the text, expressed in micromolar.2FloatμM
34Standard Error of Km [LYPLA2 (no test compound)]Standard error of the mean for the Km value.2Float
35Average Initial Velocity at 0 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 0 uM substrate concentration.2Float
36Standard Error of Initial Velocity at 0 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 0 uM substrate concentration.2Float
37Average Initial Velocity at 0 uM substrate [LYPLA2 (no test compound)] [2] (0μM**)Average initial velocity at 0 uM substrate concentration. [2]2Float
38Standard Error of Initial Velocity at 0 uM substrate [LYPLA2 (no test compound)] [2]Standard Error of average initial velocity at 0 uM substrate concentration. [2]2Float
39Average Initial Velocity at 2.5 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 2.5 uM substrate concentration.2Float
40Standard Error of Initial Velocity at 2.5 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 2.5 uM substrate concentration.2Float
41Average Initial Velocity at 5 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 5 uM substrate concentration.2Float
42Standard Error of Initial Velocity at 5 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 5 uM substrate concentration.2Float
43Average Initial Velocity at 7.5 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 7.5 uM substrate concentration.2Float
44Standard Error of Initial Velocity at 7.5 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 7.5 uM substrate concentration.2Float
45Average Initial Velocity at 10 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 10 uM substrate concentration.2Float
46Standard Error of Initial Velocity at 10 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 10 uM substrate concentration.2Float
47Average Initial Velocity at 10 uM substrate [LYPLA2 (no test compound)] [2] (0μM**)Average initial velocity at 10 uM substrate concentration. [2]2Float
48Standard Error of Initial Velocity at 10 uM substrate [LYPLA2 (no test compound)] [2]Standard Error of average initial velocity at 10 uM substrate concentration. [2]2Float
49Average Initial Velocity at 12.5 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 12.5 uM substrate concentration.2Float
50Standard Error of Initial Velocity at 12.5 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 12.5 uM substrate concentration.2Float
51Average Initial Velocity at 15 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 15 uM substrate concentration.2Float
52Standard Error of Initial Velocity at 15 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 15 uM substrate concentration.2Float
53Average Initial Velocity at 17.5 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 17.5 uM substrate concentration.2Float
54Standard Error of Initial Velocity at 17.5 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 17.5 uM substrate concentration.2Float
55Average Initial Velocity at 20 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 20 uM substrate concentration.2Float
56Standard Error of Initial Velocity at 20 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 20 uM substrate concentration.2Float
57Average Initial Velocity at 20 uM substrate [LYPLA2 (no test compound)] [2] (0μM**)Average initial velocity at 20 uM substrate concentration. [2]2Float
58Standard Error of Initial Velocity at 20 uM substrate [LYPLA2 (no test compound)] [2]Standard Error of average initial velocity at 20 uM substrate concentration. [2]2Float
59Average Initial Velocity at 30 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 30 uM substrate concentration.2Float
60Standard Error of Initial Velocity at 30 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 30 uM substrate concentration.2Float
61Average Initial Velocity at 40 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 40 uM substrate concentration.2Float
62Standard Error of Initial Velocity at 40 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 40 uM substrate concentration.2Float
63Average Initial Velocity at 40 uM substrate [LYPLA2 (no test compound)] [2] (0μM**)Average initial velocity at 40 uM substrate concentration. [2]2Float
64Standard Error of Initial Velocity at 40 uM substrate [LYPLA2 (no test compound)] [2]Standard Error of average initial velocity at 40 uM substrate concentration. [2]2Float
65Average Initial Velocity at 80 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 80 uM substrate concentration.2Float
66Standard Error of Initial Velocity at 80 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 80 uM substrate concentration.2Float
67Average Initial Velocity at 100 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 100 uM substrate concentration.2Float
68Standard Error of Initial Velocity at 100 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 100 uM substrate concentration.2Float
69Average Initial Velocity at 140 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 140 uM substrate concentration.2Float
70Standard Error of Initial Velocity at 140 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 140 uM substrate concentration.2Float
71Average Initial Velocity at 160 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 160 uM substrate concentration.2Float
72Standard Error of Initial Velocity at 160 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 160 uM substrate concentration.2Float
73Average Initial Velocity at 180 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 180 uM substrate concentration.2Float
74Standard Error of Initial Velocity at 180 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 180 uM substrate concentration.2Float
75Average Initial Velocity at 200 uM substrate [LYPLA2 (no test compound)] (0μM**)Average initial velocity at 200 uM substrate concentration.2Float
76Standard Error of Initial Velocity at 200 uM substrate [LYPLA2 (no test compound)]Standard Error of average initial velocity at 200 uM substrate concentration.2Float

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

Classification
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