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BioAssay: AID 1623

qHTS Assay for Lipid Storage Modulators: Summary

NCGC Assay Overview: Storing lipids as a reservoir for energy or the anabolism of elementary metabolites is a common feature of probably all cells and is conserved from bacteria to humans. The universal cellular lipid storage organelle is the so-called lipid storage droplet (LD). Although ubiquitous, LDs share a simple structure composed of a hydrophobic core that harbors the storage lipids, more ..
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 Related BioAssays
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AID: 1623
Data Source: NCGC (LDSA477)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-03-25
Modify Date: 2011-03-16

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: Chemical Probe: 1    Active: 1
Related Experiments
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AIDNameTypeComment
1519qHTS Assay for Lipid Storage ModulatorsConfirmatorydepositor-specified cross reference: qHTS Assay for Lipid Storage Modulators: exploratory library data
1547Secondary Assay for lipid storage modulators. NEFA Incorporation/Release.Otherdepositor-specified cross reference: Secondary Assay for Lipid Storage Modulators: NEFA Incorporation/Release
1561Secondary Assay for lipid storage modulators. CytotoxcityConfirmatorydepositor-specified cross reference: Secondary Assay for Lipid Storage Modulators: Cell-Titer Glo Cytotoxicity in S3 Cells
1569Confirmation Concentration-Response Assay for lipid storage modulatorsConfirmatorydepositor-specified cross reference: Confirmation Assay for Lipid Storage Modulators
2685qHTS Assay for Lipid Storage Modulators in Drosophila S3 CellsConfirmatorydepositor-specified cross reference: qHTS Assay for Lipid Storage Modulators
488900Secondary Assay for lipid storage modulators: Hela cell LDSA assay for probe SARConfirmatorydepositor-specified cross reference: Secondary Assay for Lipid Storage Modulators: LDSA in Hela Cells (for probe SAR)
488908Secondary Assay for lipid storage modulators: Cytotoxcity for probe SARConfirmatorydepositor-specified cross reference: Secondary Assay for Lipid Storage Modulators: Cell-Titer Glo Cytotoxicity in S3 Cells (for probe SAR
488913Confirmation Concentration-Response Assay for lipid storage modulators: for probe SARConfirmatorydepositor-specified cross reference: Confirmation Assay for S3 Lipid Storage Modulators (for probe SAR)
492960Secondary Assay for lipid storage modulators: HepG2 cell LDSA assay for probe SARConfirmatorydepositor-specified cross reference: Secondary Assay for Lipid Storage Modulators: LDSA in HepG2 Cells (for probe SAR)
504432Confirmation Concentration-Response Assay for lipid storage modulators: for probe SAR round 2Confirmatorydepositor-specified cross reference: SAR round 2, primary assay
504433Secondary Assay for lipid storage modulators: Cytotoxcity for probe SAR round 2Confirmatorydepositor-specified cross reference: SAR round 2, secondary
504434Secondary Assay for lipid storage modulators: AML12 cell LDSA assay for probe SARConfirmatorydepositor-specified cross reference: Secondary LDSA assay
652175qHTS Assay for Lipid Storage Modulators: S3 Assay against Probe and AnalogsConfirmatorydepositor-specified cross reference
652180qHTS Assay for Lipid Storage Modulators: 3T3L1 Assay against Probe and AnalogsConfirmatorydepositor-specified cross reference
652183qHTS Assay for Lipid Storage Modulators: Differentiation Assay against Probe and AnalogsConfirmatorydepositor-specified cross reference
652184qHTS Assay for Lipid Storage Modulators: Extended Characterization SummarySummarydepositor-specified cross reference
652283qHTS Assay for Lipid Storage Modulators: COS7 Assay against Probe and AnalogsConfirmatorydepositor-specified cross reference
686935qHTS Assay for Lipid Storage Modulators: CytotoxicityAssay against Probe and AnalogsConfirmatorydepositor-specified cross reference
Description:
NIH Molecular Libraries Probe Production Centers Network [MLPCN]
NIH Chemical Genomics Center [NCGC]
MLPCN Grant: 1 R03 MH085686-01
Assay Submitter (PI): Beller, Mathias; Max-Planck-Institut fur Biophysikalische Chemie

NCGC Assay Overview: Storing lipids as a reservoir for energy or the anabolism of elementary metabolites is a common feature of probably all cells and is conserved from bacteria to humans. The universal cellular lipid storage organelle is the so-called lipid storage droplet (LD). Although ubiquitous, LDs share a simple structure composed of a hydrophobic core that harbors the storage lipids, which is shielded by a droplet-specific phospholipid monolayer to which proteins are attached. The current model of LD biogenesis involves an incorporation of the lipid core into the membrane leaflets of the endoplasmic reticulum (ER) followed by a subsequent budding-like maturation of a LD, which ultimately pinches off. Once released, LD volume can increase by localized lipogenesis or fusion of existing droplets. Storage lipids are re-mobilized enzymatically by lipase activity. Lipase regulation in the adipocyte is heavily studied and involves multiple components including catecholamine signaling, the LD-associated proteins Perilipin and comparative gene identification-58 (CGI-58) and at least two lipases named hormone sensitive lipase (HSL) and adipocyte triglyceride lipase (ATGL). We developed a laser-scanning cytometer assay to enable 1,536-well screening and combined the results of the small molecules screen with an RNAi database based on lipid storage [1]. We identified Exo1in the primary screen (AID 1519 and 2685) and several analogs (AID 1569) [2] were confirmed to increase lipid storage in S3 cells. The results of both the RNAi and small molecule compound screen showed that positive regulation of lipolysis by the COPI retrograde vesicle trafficking pathway is involved with lipid over-storage [1].

The compound (CID_310557, ML084) was identified as a lipid storage activator.
Protocol
Please refer to other AIDs (1519, 1569, 1561, 1547 and 2685) for detailed assay protocols.
Comment
This summary is written for the purposes of summarizing the activities of the probe, Exo1, identified in this project. A weakly active analog (CID: 2116512) is shown in AID 1569 (see also ref [2]). MLSCN probes are given a score of 100.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 4
MLP Probe ML# for probe 1: ML220
PubChem Substance ID (SID) for probe 1: 99460839
PubChem Compound ID (CID) for probe 1: 46947860
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK153217/ (ID: 3046430)
Grant number for probe 1: MH085686-01
MLP Probe ML# for probe 2: ML360
PubChem Substance ID (SID) for probe 2: 161004695
PubChem Compound ID (CID) for probe 2: 70789742
Probe type for probe 2: Inhibitor
IC50/EC50 (nM) for probe 2: 0.011
Target for probe 2: 3T3L1
Disease relevance for probe 2: Diabetes
Anti-target for probe 2: Viablility Assay
Fold selectivity for probe 2: >20
NCBI Book chapter link for probe 2: http://www.ncbi.nlm.nih.gov/books/NBK179824/ (ID: 3069900)
Grant number for probe 2: MH085686
MLP Probe ML# for probe 3: ML206
PubChem Substance ID (SID) for probe 3: 99381576
PubChem Compound ID (CID) for probe 3: 16192366
NCBI Book chapter link for probe 3: http://www.ncbi.nlm.nih.gov/books/NBK153217/ (ID: 3046430)
MLP Probe ML# for probe 4: ML219
PubChem Substance ID (SID) for probe 4: 99460848
PubChem Compound ID (CID) for probe 4: 46947845
NCBI Book chapter link for probe 4: http://www.ncbi.nlm.nih.gov/books/NBK153217/ (ID: 3046430)
NCBI Book chapter title for probe 1: Modulators of Lipid Storage
NCBI Book chapter title for probe 2: ML360, A Potent Inhibitor of Lipid Droplet Formation
NCBI Book chapter title for probe 3: Modulators of Lipid Storage
NCBI Book chapter title for probe 4: Modulators of Lipid Storage
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ML#Molecular library probe numberString
2PhenotypeIndicates type of activity observed based on the compound activity across various assays tested.String
3PotencyConcentration at which compound exhibits half-maximal efficacy, AC50. Extrapolated AC50s also include the highest efficacy observed and the concentration of compound at which it was observed.FloatμM
4NEFA Incorporation/Release Assay PhenotypeIndicates type of activity observed in NEFA incorporation/release secondary assay.String
5CytotoxicityIndicates type of activity observed in cytotoxicity assay.String
Additional Information
Grant Number: 1 R03 MH085686-01

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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