BAY-876

BAY-876 is a selective glucose transporter 1 (GLUT1) inhibitor with IC₅₀ of 2 nM^[1]. The IC₅₀ of BAY-876 for GLUT2, GLUT3 and GLUT4 are 10.8, 1.67 and 0.29μM, respectively^[1]. BAY-876 blocks glucose transport into tumor cells by inhibiting GLUT activity, thereby effectively inhibiting glucose uptake and tumor cell growth ^[2].

In vitro, BAY-876 (75nM) treated SKOV-3, OVCAR-3, HEY and A2780 cells for 72h and had a growth inhibitory effect on SKOV-3, OVCAR-3 and HEY cells, but not on A2780 cells ^[3] . BAY-876 (10 nM, 25 nM, 50 nM) treated CD4⁺ T cells and macrophages for 24 hours, significantly weakening the glucose uptake of cells and reducing the levels of inflammatory factors ^[4]. BAY-876 (10-1000µM) treated the renal adenocarcinoma 786-O cell line for 96 hours and significantly inhibited cell proliferation, with an IC₅₀ of 53.56µM ^[5].

In vivo, BAY-876 (0, 1.5, 3.0, and 4.5 mg/kg/day) dose-dependently reduced tumor volume in NSG mice harboring SKOV-3 xenografts administered orally for 4 weeks and was effective in mice. Body weight has no effect ^[3]. BAY-876 (5 mg/kg/day) was administered orally for 2 days to mice bearing MHCC 97-H xenografts, which significantly inhibited tumor tissue formation and glucose uptake by cells in the tissue ^[6].

References:
[1] Siebeneicher H, Cleve A, Rehwinkel H, et al. Identification and optimization of the first highly selective GLUT1 inhibitor BAY‐876[J]. ChemMedChem, 2016, 11(20): 2261-2271.
[2] Kopitz C, Toschi L, Algire C, et al. Pharmacological characterization of BAY-876, a novel highly selective inhibitor of glucose transporter (GLUT)-1 in vitro and in vivo[J]. Cancer Research, 2016, 76(14_Supplement): 4746-4746.
[3] Ma Y, Wang W, Idowu M O, et al. Ovarian cancer relies on glucose transporter 1 to fuel glycolysis and growth: anti-tumor activity of BAY-876[J]. Cancers, 2018, 11(1): 33.
[4] Chen Z, Vaeth M, Eckstein M, et al. Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages[J]. European Journal of Pharmacology, 2023, 945: 175552.
[5] Peshraw Salih Hamadamin, et al. Exploring the anticancer potential of hydrogen sulfide and BAY876 on clear cell renal cell carcinoma cells: Uncovering novel mutations in VHL and KDR genes among ccRCC patients[J]. Molecular and Clinical Oncology, 2024.
[6] Yang H, Zhang M Z, Sun H, et al. A novel microcrystalline BAY-876 formulation achieves long-acting antitumor activity against aerobic glycolysis and proliferation of hepatocellular carcinoma[J]. Frontiers in Oncology, 2021, 11: 783194.

BAY-876是一种选择性的葡萄糖转运蛋白1（GLUT1）抑制剂，IC₅₀ 为2nM^[1]。BAY-876 对GLUT2，GLUT3和 GLUT4 的IC₅₀分别为10.8、1.67、0.29μM^[1]。BAY-876通过抑制GLUT活性，阻止葡萄糖转运进入肿瘤细胞，从而有效抑制葡萄糖摄取和肿瘤细胞生长^[2]。

在体外，BAY-876（75nM）处理SKOV-3，OVCAR-3，HEY和A2780细胞72h，对SKOV-3，OVCAR-3和HEY细胞中具有生长抑制作用，但在A2780细胞中没有^[3]。BAY-876（10 nM、25 nM、50 nM）处理CD4⁺ T细胞和巨噬细胞24h，显著减弱了细胞的葡萄糖摄取，且降低了炎症因子水平^[4]。BAY-876（10-1000µM）处理肾腺癌786-O细胞系96h，显著抑制细胞增值，IC₅₀为53.56µM^[5]。

在体内，BAY-876（0、1.5、3.0和4.5 mg/kg/day）通过口服治疗携带SKOV-3异种移植物的NSG小鼠4周，剂量依赖性地减小了肿瘤体积，且对小鼠体重没有影响^[3]。BAY-876（5 mg/kg/day）通过口服治疗携带MHCC 97-H异种移植物的小鼠2天，显著抑制了肿瘤组织生成和组织中细胞的葡萄糖摄取^[6]。