Fatostatin A is a novel, potent and cell permeable inhibitor of SREBP (Sterol regulatory element-binding protein) activation with anticancer activity. It acts by directly binding SCAP and blocking its ER-to-Golgi transport with IC50 of 2.5 and 10 μM in mammalian cells. Fatostatin blocks ER exit of SCAP and showed that inhibition is independent of insulin-induced gene proteins, which function to retain the SCAP-SREBP complex in the ER. Fatostatin potently inhibited cell growth, but unexpectedly exogenous lipids failed to rescue proliferation of fatostatin-treated cells. Furthermore, fatostatin inhibited growth of cells lacking SCAP. In summary, fatostatin inhibited SREBP activation, but fatostatin additionally inhibited cell proliferation through both lipid-independent and SCAP-independent mechanisms, possibly by general inhibition of ER-to-Golgi transport. Sterol regulatory element-binding protein (SREBP) transcription factors are central regulators of cellular lipid homeostasis and activate expression of genes required for fatty acid, triglyceride, and cholesterol synthesis and uptake. SREBP cleavage activating protein (SCAP) plays an essential role in SREBP activation by mediating endoplasmic reticulum (ER)-to-Golgi transport of SREBP. In the Golgi, membrane-bound SREBPs are cleaved sequentially by the site-1 and site-2 proteases. Recent studies have shown a requirement for the SREBP pathway in the development of fatty liver disease and tumor growth, making SCAP a target for drug development.

References: Biochim Biophys Acta. 2015 Nov;1852(11):2432-41.; J Lipid Res. 2016 Aug;57(8):1564-73.

These protocols are for reference only. InvivoChem does not independently validate these methods.