Fatostatin

Fatostatin (125B11), a diarylthiazole derivative, is a specific inhibitor of Sterol regulatory element binding proteins (SREBPs) activation. Fatostatin binds to SCAP (SREBP cleavage-activating protein), and inhibits the ER-Golgi translocation of SREBPs. Fatostatin suppresses growth and enhances apoptosis in cancer cells.

Fatostatin impairs the activation process of sterol regulatory element binding proteins (SREBPs), thereby decreasing the transcription of lipogenic genes in cells. Fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain.^[1]

CHO-K1 cells are plated out onto a 96-well plate in medium A. The cells are transiently cotransfected with pCMV-PLAP-BP2, pCMV-SCAP, and pAc-b-gal, using Lipofectamine reagent. After incubation for 5 hr, the cells are washed with PBS and then incubated in medium B, in the absence or presence of fatostatin (20 μM) or sterols (10 μg/mL cholesterol and 1 μg/mL 25-hydroxycholesterol). After 20 hr of incubation, an aliquot of the medium is assayed for secreted alkaline phosphatase activity. The cells in each well are lysed and used for measurement of b-galactosidase activities. The alkaline phosphatase activity is normalized by the activity of b-galactosidase.

Fatostatin blocks increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake. Fatostatin may serve as a tool for gaining further insights into the regulation of SREBP.^[1]