Autophagy Inducer, STF-62247

Autophagy Inducer, STF-62247 is a small molecule agonist that induces autophagy and selectively causes lethality in renal cell carcinoma (RCC) cells that have lost the von Hippel-Lindau (VHL) tumor suppressor activity (IC₅₀ = 625 nM). It significantly reduces the growth rate of tumors formed from VHL-deficient cells in mice. STF-62247 induces cytotoxicity in VHL-positive RCC cells only at higher concentrations (IC₅₀ = 16 μM). 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 μM in RCC4 and RCC4/VHL killing, respectively) and in mice. 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.