7211760086

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7211760086

Autophagy_Inducer

N-(3-Methylphenyl)-4-(4-pyridinyl)-2-thiazolamine (STF-62247)

selectively induces cell death in VHL-deficient cells

OTAVAchemicals Catalogue Number: 7211760086

CAS Registry Number: 315702-99-9

Purity: 95%+ (HPLC)

Ref.: Turcotte et al. A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy. Cancer Cell (2008), 14, 90-102


Abstract: Renal cell carcinomas (RCCs) are refractory to standard therapies. The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in 75% of RCCs. By screening for small molecules selectively targeting VHL-deficient RCC cells, we identified STF-62247. STF-62247 induces cytotoxicity and reduces tumor growth of VHL-deficient RCC cells compared to genetically matched cells with wild-type VHL. STF-62247-stimulated toxicity occurs in a HIF-independent manner through autophagy. Reduction of protein levels of essential autophagy pathway components reduces sensitivity of VHL-deficient cells to STF-62247. Using a yeast deletion pool, we show that loss of proteins involved in Golgi trafficking increases killing by STF-62247. Thus, we have found a small molecule that selectively induces cell death in VHL-deficient cells, representing a paradigm shift for targeted therapy.

 

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