STF-31 is a selective inhibitor of glucose transporter 1 (GLUT1), with an IC50 of 1 μΜ [1].
The inactivated von Hippel-Lindau (VHL) tumor suppressor gene drives renal cell carcinomas (RCCs) development, which imparts the reliance on the GLUT1 and aerobic glycolysis. Compounds of the 3-series, exemplified by STF-31, selectively kills RCCs by specifically targeting glucose uptake through GLU1, on which is the unique dependence of these cells for survival.
STF-31 (0.01-10 μΜ; 10 days) is specifically toxic to RCC4 cells without VHL, while wild-type RCC4 cells (RCC4/VHL) are relatively unaffected. Wild-type RCC4 cells treated with STF-31 (5 μΜ; 10 days) largely recovery, while RCC4 cells dose not on the same condition. No evidence proved the drug-induced cells autophagy, apoptosis, or DNA damages, but wild-type RCC4 cells underwent necrotic cell death in response to STF-31 by the ability of the cells to exclude trypan blue [1].
Soluble analog of STF-31 (11.6 mg/kg; i.p.) treatment delayed tumor growth in mice with VHL-deficient RCC tumor xenografts [1]. STF-31 (10 mg/kg; i.p.; twice daily for 2 days, followed by once daily for another 3 days) did not affect normal mice body weight, behavior and Scotopic electroretinography (ERG) responses. STF-31 reduced light-induced CX3CR1gfp/+ mice microglial activation and retinal degeneration [2].
Reference:
[1] Chan D A, Sutphin P D, Nguyen P, et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med. 2011, 3(94): 94ra70.
[2] Wang L X, Pavlou S, Du X, et al. Glucose transporter 1 critically controls microglial activation through facilitating glycolysis. Mol Neurodegener. 2019, 14(1): 2.
