AbMole丨BAY-876：GLUT1抑制剂，在代谢调控和肿瘤研究中的应用

BAY-876是一种高选择性葡萄糖转运蛋白1（GLUT1）抑制剂，通过靶向抑制GLUT1介导的葡萄糖摄取，在多种研究中展现出显著的代谢调控与抗增殖作用。其作用机制主要包括：（1）直接抑制GLUT1蛋白表达，如Western blot分析显示其在人结直肠癌细胞系（HCT116、DLD1、COLO205、LoVo）中可降低GLUT1蛋白水平[1]。（2）通过阻断糖酵解通路，诱导线粒体呼吸增强和活性氧（ROS）积累，导致细胞凋亡率上升，在体外实验中2 nM BAY-876即可抑制高糖诱导的GLUT1 mRNA和蛋白表达[2]。（3）与EGFR信号通路相互作用：BAY-876能通过抑制EGFR下游通路增强其它抑制剂（如Osimertinib ）的敏感性[3]。

BAY-876（AbMole，M8659）在多种细胞系中表现出剂量依赖性的抑制效果。例如，在卵巢癌细胞中，BAY-876（CAS No.：1799753-84-6）通过阻断糖酵解和锚定非依赖性生长，显著抑制细胞增殖[4]。0.05 μM的BAY-876能特异性抑制GLUT1介导的肌肉细胞葡萄糖摄取[5]。BAY-876还能显著抑制砷酸盐处理的L-02肝细胞中GLUT1膜定位及葡萄糖摄取[6]。在小鼠异种移植模型中，BAY-876表现出显著的抗肿瘤活性。例如，在结直肠癌移植瘤中，BAY-876治疗组显示GLUT1表达抑制和肿瘤生长减缓[1]。BAY-876还被用于研究代谢重编程与免疫调控之间的关联。例如，在CD4 +T细胞中，GLUT1抑制可减少20%的IFN-γ分泌，同时巨噬细胞中TNF分泌降低27%[7]。

参考文献及鸣谢

[1] Hayashi, M.; Nakamura, K.; Harada, S.; et al. GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells. BMC cancer 2025, 25 (1), 716.

[2] Larenas, P. E.; Cardenas, P.; Aguirre-Delgadillo, M.; et al. GLUT1 and prorenin receptor mediate differential regulation of TGF-beta and CTGF in renal inner medullary collecting duct cells during high glucose conditions. Biological research 2024, 57 (1), 81.

[3] Xie, Z.; Zhou, Z.; Chen, S.; et al. GLUT1 sensitizes tumor cells to EGFR-TKIs by binding with activated EGFR and regulating its downstream signaling pathways. Cell communication and signaling : CCS 2025, 23 (1), 247.

[4] 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. Cancers 2018, 11 (1).

[5] McMillin, S. L.; Evans, P. L.; Taylor, W. M.; et al. Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake. Biomolecules 2022, 12 (12).

[6] Lou, Q.; Zhang, M.; Yang, Y.; et al. Low-dose arsenic trioxide enhances membrane-GLUT1 expression and glucose uptake via AKT activation to support L-02 cell aberrant proliferation. Toxicology 2022, 475, 153237.

[7] Chen, Z.; Vaeth, M.; Eckstein, M.; et al. Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages. European journal of pharmacology 2023, 945, 175552.