Summary Assay for the inhibition of Hepatic Lipid Droplet Formation
Medical researchers world-wide now use the term "epidemic" or "pandemic" to describe the alarming incidence of obesity in modern society, which is estimated to occur in 30% of the general US population. Perhaps, most alarming is the high incidence of obesity in children and adolescents, which indicates that medical problems associated with obesity (e.g., diabetes, metabolic syndrome, and heart more ..
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R03 MH083261-01A1
Assay Provider: Dr. Patrick M. McDonough, Vala Sciences Inc.
Medical researchers world-wide now use the term "epidemic" or "pandemic" to describe the alarming incidence of obesity in modern society, which is estimated to occur in 30% of the general US population. Perhaps, most alarming is the high incidence of obesity in children and adolescents, which indicates that medical problems associated with obesity (e.g., diabetes, metabolic syndrome, and heart disease) will increase in the foreseeable future, as obesity often increases with age. The dominant cellular basis for obesity is increased accumulation of triglycerides in lipid droplets within the cell. The two major cell types in which lipid droplet formation leads to pathological problems are adipocytes and hepatocytes.
The overall goal of this project is to identify chemical probes for inhibiting lipid droplet formation in hepatocytes. Identification of such compounds will better our understanding of the biochemical/molecular pathways that lead to the development of fatty liver disease, and may identify lead compounds for consideration for therapeutic development.
1) Hill, J. O., Peters, J. C., Wyatt, H. R. 2007. The role of public policy in treating the epidemic of global obesity, Clin Pharmacol Ther. 2007 May;81(5):772-5.
2) Fujimoto, Y., Itabe, H., Kinoshita, T., Homma, K. J., Onoduka, et al. 2007, Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7. J. Lipid Res. 48:1280-1292
3) Reddy, J. K., Rao, M. S. 2006. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation, Am. J. Phsyiol. Gastrointest. Liver Physiol. 290:G852-G858
This AID is used to summarize the results of this MLPCN project. Thus far the work reported has not reached the point where probes have been identified. Probe molecules are defined as the positives of this assay and assigned a score of 100
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 2
MLP Probe ML# for probe 1: ML262
PubChem Substance ID (SID) for probe 1: 104222756
PubChem Compound ID (CID) for probe 1: 20855303
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: <70
Target for probe 1: Lipid Droplets Formation in AML12
Disease relevance for probe 1: Non-alcoholic fatty liver disease (NAFLD)
Anti-target for probe 1: AML12 HCS cytotoxicity Index < 3
Fold selectivity for probe 1: >477
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK143550/ (ID: 3036144)
Grant number for probe 1: DA026213-01
MLP Probe ML# for probe 2: ML261
PubChem Substance ID (SID) for probe 2: 103061845
PubChem Compound ID (CID) for probe 2: 9550710
NCBI Book chapter title for probe 1: Potent inhibitors of lipid droplet formation