STF-62247

Inducer of autophagy in renal cell carcinoma cells

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Background

IC50: STF-62247 inhibits tumor growth in wild-type VHL and VHL-deficient renal cell carcinoma (RCC) in a HIF-independent manner with IC50 of 16 μM and 0.625 μM, respectively.

Inactivation of the von Hippel-Lindau (VHL) tumor inhibitor gene results in a large number of renal cell carcinomas (RCCs) and is closely linked to a high degree of vascularization and poor prognosis. STF-62247 is reported to exhibit selectively cytotoxic toward VHL-deficient cells in vitro and in vivo. [1]

In vitro: In vitro study demonstrated that STF-62247 exhibited selectively cytotoxicity and tumor growth inhibitory activity towards wild-type VHL and VHL-deficient renal cell carcinoma (RCC) in a HIF-independent manner with IC50 of 16 μM and 0.625 μM, respectively. In addion, STF-62247 also resulted in cell apoptosis by inducing acidification and increasing autophagy in VHL-deficient cells. [1]

In vivo: Animal experiments for STF-62247 activity were performed according to institutional and national guidelines and approved by Stanford University's Administrative Panel on Laboratory Animal Care. Based on an in vivo mouse model, it was found that intraperitoneal injection of STF-62247 at a dose of 8 mg/kg significantly inhibited tumor growth of VHL-deficient SN12C tumor cells. [1]

Clinical trial: So far, no clinical trial has been conducted.

Reference:
[1]Turcotte S, Chan DA, Sutphin PD, Hay MP, Denny WA and Giaccia AJ.? A molecule targeting vhl-deficient renal cell carcinoma that induces autophagy. Cancer Cell. 2008 Jul; 14: 90-102.