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Description

A cell-permeable autophagy inducer that selectively induces non-apoptotic cell death in VHL- (von Hippel-Lindau) deficient, but not VHL-expressing, renal carcinoma cells both in vitro (IC50 = 0.625 and 16 µ,M in RCC4 and RCC4/VHL killing, respectively) and in mice in vivo (>90% 786-O tumor growth suppression, 8 mg/kg via daily i.p.). Although STF-62247 induces autophagy regardless of cellular VHL-expression level, STF-62247 treatment is shown to result in more enhanced/acidified autolysomes formation in VHL-deficient cells, implicating an important role of VHL in maintaining normal vesicular trafficking between ER, TNG, and lysosomes.