WZB117 is a small molecule inhibitor targeting glucose transporter 1 (GLUT1) [1]. WZB117 reduces glucose uptake in cancer cells, lowers intracellular ATP levels, and activates AMPK, which in turn triggers cell cycle arrest, senescence, and necrosis [2-3]. WZB117 is mainly used in the field of tumor research to inhibit the glucose metabolism and growth of cancer cells [4].
In A375 and SK-MEL-28 cells, Apatinib combined with WZB117 (0-160μM; 24h, 48h, 72h) showed synergistic cell growth inhibitory effects on cell [5]. In PANC-1 cells, WZB117 (10μM, 25μM; 24h) significantly reduced glycogenolysis in cells in a dose-dependent manner [6]. In SH-SY5Y cells, WZB117 (1-30μM; 72h) treatment reduces tumor cell viability and downregulates GLUT1 protein levels [7].
In P. berghei ANKA-infected mice model, WZB117 (10mg/kg; iv; 11d) effectively inhibits the growth of blood-stage parasites [8]. In PANC-1 CSLC subcutaneous tumor mice model, WZB117 (20mg/kg; ip; 20d) inhibits the tumor-initiating ability of PANC-1 CSLCs in vivo [9].
References:
[1]. Ojelabi OA, Lloyd KP, Simon AH, et al. WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) inhibits GLUT1-mediated sugar transport by binding reversibly at the exofacial sugar binding site. Journal of Biological Chemistry. 2016 Dec 1;291(52):26762-26772.
[2]. Liu Y, Cao Y, Zhang W, et al. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Molecular cancer therapeutics. 2012 Aug 1; 11(8): 1672-1682.
[3]. Ojelabi O, DeZutter J, Lloyd K, et al. Novel small molecule, WZB117, competitively inhibit GLUT1‐mediated glucose transport to halt cancer growth. The FASEB Journal. 2016 Apr; 30: 1099.
[4]. Qian Y, Shriwas P, Wang X, et al. Screening and identification of new generation glucose transporter inhibitors as anticancer therapeutics. Cancer Research. 2017 Jul 1; 77(13_Supplement): 1157.
[5]. Zhang RS, Li ZK, Liu J, et al. WZB117 enhanced the anti-tumor effect of apatinib against melanoma via blocking STAT3/PKM2 axis. Frontiers in Pharmacology. 2022 Sep 16; 13: 976117.
[6]. Poonprasartporn A, Xiao J, Chan KA. A study of WZB117 as a competitive inhibitor of glucose transporter in high glucose treated PANC-1 cells by live-cell FTIR spectroscopy. Talanta. 2024 Jan 1; 266: 125031.
[7]. Peng Y, Xing SN, Tang HY, et al. Influence of glucose transporter 1 activity inhibition on neuroblastoma in vitro. Gene. 2019 Mar 20; 689: 11-17.
[8]. Wei M, Lu L, Sui W, et al. Inhibition of GLUTs by WZB117 mediates apoptosis in blood-stage Plasmodium parasites by breaking redox balance. Biochemical and biophysical research communications. 2018 Sep 5; 503(2): 1154-1159.
[9]. Shibuya K, Okada M, Suzuki S, et al. Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells. Oncotarget. 2014 Nov 26; 6(2): 651.
WZB117是一种靶向葡萄糖转运蛋白1（GLUT1）的小分子抑制剂 [1]。WZB117可降低癌细胞对葡萄糖的摄取，降低细胞内ATP水平，并激活AMPK，进而引发细胞周期停滞、衰老和坏死 [2-3]。WZB117主要用于肿瘤研究领域，抑制癌细胞的葡萄糖代谢和生长 [4]。
在A375和SK-MEL-28细胞中，阿帕替尼与WZB117（0-160μM；24h、48h、72h）联合用药对细胞生长有协同抑制作用 [5]。在PANC-1细胞中，WZB117（10μM、25μM；24h）以剂量依赖性方式显著降低细胞糖原分解 [6]。在SH-SY5Y细胞中，WZB117（1-30μM；72h）治疗可降低肿瘤细胞活力并下调GLUT1蛋白水平 [7]。
在感染伯氏疟原虫ANKA的小鼠模型中，WZB117（10mg/kg；ip；11d）可有效抑制血液阶段寄生虫的生长 [8]。在PANC-1 CSLC皮下肿瘤小鼠模型中，WZB117（20mg/kg；ip；20d）可抑制PANC-1 CSLC在体内的肿瘤起始能力 [9]。