Wang Yuxuan, Sun Zhiqiang, Zhao Zean, Pang Jianxin, Chen Jianjun
Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510280, China.
Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
J Med Chem. 2025 Jan 23;68(2):1033-1050. doi: 10.1021/acs.jmedchem.4c02717. Epub 2025 Jan 2.
Cancer cells exhibit an accelerated glucose uptake and glycolysis. The transmembrane uptake of glucose requires specific carrier proteins, such as glucose transporters (GLUTs) and sodium-coupled glucose cotransporters (SGLTs). GLUTs transport glucose independently of the energy supply and have become promising targets for cancer therapy. This Perspective mainly focuses on the current research progress and design strategy of GLUT inhibitors, particularly those targeting class I (GLUT1-4). To the best of our knowledge, this is the first systematic interpretation of the research progress, opportunities, and challenges faced in the development of GLUT inhibitors from a medicinal chemistry perspective. We hope that this Perspective will provide insights into the development of GLUT inhibitors, offering a feasible approach to cancer therapy.
癌细胞表现出加速的葡萄糖摄取和糖酵解。葡萄糖的跨膜摄取需要特定的载体蛋白，如葡萄糖转运蛋白（GLUTs）和钠偶联葡萄糖共转运蛋白（SGLTs）。GLUTs独立于能量供应转运葡萄糖，已成为癌症治疗的有前景的靶点。本综述主要关注GLUT抑制剂的当前研究进展和设计策略，特别是针对I类（GLUT1 - 4）的抑制剂。据我们所知，这是从药物化学角度对GLUT抑制剂开发中所面临的研究进展、机遇和挑战的首次系统解读。我们希望本综述能为GLUT抑制剂的开发提供见解，为癌症治疗提供一种可行的方法。
