Modulators of Lipid Storage

Excerpt

The primary goal of the project was the identification of chemical probes decreasing the storage lipid content of cells. For this purpose, a cell-based assay using embryonic Drosophila melanogaster cells called “S3” was developed. Cells were incubated with the free fatty acid oleate to induce storage lipid deposition. Lipids are stored in specialized organelles, the so-called lipid droplets, which were stained with the lipophilic dye BODIPY493/503 (Invitrogen/Molecular Probes). We identified three unique chemotypes showing potent lipid droplet reduction phenotypes in the S3 cell based assay. The three probes identified, ML206, ML219 and ML220, had EC₅₀s of 8, 2 and 705 nM, respectively. While ML206 showed little translation into mammalian cell lines, both ML219 and ML220 showed moderate translation into acute myeloid leukemia (AML)12 cells.