|qHTS Assay for Lipid Storage Modulators: Summary - BioAssay 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 ..
Depositor Specified Assays
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 . We identified Exo1in the primary screen (AID 1519 and 2685) and several analogs (AID 1569)  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 .
The compound (CID_310557, ML084) was identified as a lipid storage activator.
Please refer to other AIDs (1519, 1569, 1561, 1547 and 2685) for detailed assay protocols.
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 ). MLSCN probes are given a score of 100.
Data Table (Concise)