The sterol regulatory-element binding protein (SREBPs) are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion, and migration, and it arrests cancer cells in G2/M phase[3]. Fatostatin hydrobromide (125B11 hydrobromide) impairs the activation of SREBP-1 and SREBP-2. Fatostatin hydrobromide binds to SCAP (SREBP cleavage-activating protein), and inhibits the ER-Golgi translocation of SREBPs. Fatostatin hydrobromide decreases the transcription of lipogenic genes in cells. Fatostatin hydrobromide possesses antitumor properties, and lowers hyperglycemia in ob/ob mice. Fatostatin hydrobromide (0.1-1 μM; 3 days) inhibits the androgen-independent prostate cancer cell proliferation (IC50=0.1μM) in an independent of the known IGF1-signaling pathway. Fatostatin hydrobromide inhibits insulin-induced adipogenesis of 3T3-L1 cells[4]. Fatostatin hydrobromide (30 mg/kg; 150 mL; i.p.; daily for 28 days) reduces adiposity, ameliorates fatty liver by reducing triglyceride (TG) storage, and lowers hyperglycemia in ob/ob mice[5]. Fatostatin could induce ER degradation by K48-linked polyubiquitination, which was the key mechanism contributing to tamoxifen inhibition of PI3K-AKT-mTOR signalling in breast cancer[6].
Fatostatin HBr 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
CHO-K1 cells
Function assay
20 h
Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay, IC50=5.6 μM
21561152
mouse hepatocytes
1 uM
Function assay
90 mins
Metabolic stability in mouse hepatocytes at 1 uM after 90 mins by LC-MS/MS analysis
Inhibition of SREBP2 activation expressed in CHO-K1 cells co-transfected with pSRE-Luc plasmid assessed as inhibition of luciferase expression after 20 hrs by luciferase reporter gene assay, IC50=5.6 μM
21561152
mouse hepatocytes
1 uM
Function assay
90 mins
Metabolic stability in mouse hepatocytes at 1 uM after 90 mins by LC-MS/MS analysis
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