STF 31 is a cell-permeable inhibitor of glucose transporter 1 (GLUT1) with an IC₅₀ of 1μM[1]. GLUT1 is a key transporter responsible for glucose uptake and plays an essential role in maintaining glycolytic metabolism[2]. STF 31 can inhibit nicotinamide phosphoribosyltransferase (NAMPT), thereby disrupting glycolysis and inducing cytotoxicity[3].
In vitro, STF 31 (0-10μM) treatment inhibited the glucose uptake capacity of B6M7 cells in a dose-dependent manner within 24h without significantly affecting cell viability[4]. STF 31 (30μM) treatment of MCF-7 cells for 48h significantly suppressed glycolysis and induced apoptosis[5]. STF 31 (2, 4, and 8μM) treatment of rheumatoid arthritis fibroblast-like synoviocytes (RAFLs) for 24-72h inhibited cell proliferation in a time- and dose-dependent manner[6].
In vivo, STF 31 (10mg/kg), administered via intraperitoneal injection (twice daily for the first 2 days, followed by once daily for the next 3 days), had no significant effects on body weight, behavior, or ERG responses in normal mice. In a light-induced model, STF 31 significantly inhibited microglial activation in CX3CR1gfp/+ mice and alleviated retinal degeneration[4]. Intraperitoneal co-administration of STF 31 (10mg/kg) and dexamethasone in normal mice for 4h significantly promoted the accumulation of necrotic thymocytes[7].
References:
[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[J]. Sci Transl Med, 2011, 3(94).
[2] Wu Q, ba-alawi W, Deblois G, et al. GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer[J]. Nat Commun, 2020, 11(1).
[3] Adams D J, Ito D, Rees M G, et al. NAMPT Is the Cellular Target of STF 31-Like Small-Molecule Probes[J]. Acs Chem Biol, 2014, 9(10): 2247-2254.
[4] Wang L X, Pavlou S, Du X, et al. Glucose transporter 1 critically controls microglial activation through facilitating glycolysis[J]. Mol Neurodegener, 2019, 14.
[5] Xintaropoulou C, Ward C, Wise A, et al. A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models[J]. Oncotarget, 2015, 6(28): 25677-25695.
[6] Hou Hou, Lü Xing, Zhang Na, et al. Mechanism Analysis of the Effect of STF 31 on Proliferation and Apoptosis of Fibroblast-like Synoviocytes in Rheumatoid Arthritis [J]. Anatomical Research, 2022, 44(06): 525-531
[7] Morioka S, Perry JSA, Raymond MH, et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release[J]. Nature, 2018, 563(7733): 714-718.
STF 31是一种具有细胞通透性的葡萄糖转运蛋白1（GLUT1）的抑制剂，IC₅₀为1μM[1]。GLUT1是介导葡萄糖摄取的重要转运蛋白，参与维持糖酵解代谢[2]。STF 31还可抑制烟酰胺磷酸核糖转移酶（NAMPT），从而干扰糖酵解过程并产生细胞毒性[3]。
在体外，STF 31（0-10μM）处理B6M7细胞24h，可剂量依赖性抑制细胞的葡萄糖摄取能力，而对细胞存活率无明显影响[4]。STF 31（30μM）处理MCF-7细胞48h，可显著抑制糖酵解过程并诱导细胞凋亡[5]。STF 31（2、4、8μM）处理类风湿关节炎成纤维样滑膜细胞（RAFLs）24-72h，以时间和剂量依赖性方式抑制细胞增殖[6]。
在体内，STF 31（10mg/kg）通过腹腔注射给药（前2天每日两次，随后3天每日一次），对正常小鼠的体重、行为及ERG反应无明显影响。在光诱导模型中，STF 31可显著抑制CX3CR1gfp/+小鼠小胶质细胞的活化，并减轻视网膜变性[4]。STF 31（10mg/kg）与地塞米松通过腹腔联合注射正常小鼠4h，可显著促进坏死胸腺细胞的积累[7]。