Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, PR China.
Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang City, Hunan Province, PR China.
Bioorg Chem. 2021 Jul;112:104891. doi: 10.1016/j.bioorg.2021.104891. Epub 2021 Apr 8.
Tumor cells mainly provide necessary energy and substances for rapid cell growth through aerobic perglycolysis rather than oxidative phosphorylation. This phenomenon is called the "Warburg effect". The mechanism of glycolysis in tumor cells is more complicated, which is caused by the comprehensive regulation of multiple factors. Abnormal enzyme metabolism is one of the main influencing factors and inhibiting the three main rate-limiting enzymes in glycolysis is thought to be important strategy for cancer treatment. Therefore, numerous inhibitors of glycolysis rate-limiting enzyme have been developed in recent years, such as the latest HKII inhibitor and PKM2 inhibitor Pachymic acid (PA) and N-(4-(3-(3-(methylamino)-3-oxopropyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-1-yl)phenyl)propiolamide. The review focuses on source, structure-activity relationship, bioecological activity and mechanism of the three main rate-limiting enzymes inhibitors, and hopes to guide the future research on the design and synthesis of rate-limiting enzyme inhibitors.
肿瘤细胞主要通过有氧糖酵解而非氧化磷酸化为快速细胞生长提供必要的能量和物质。这种现象被称为“瓦博格效应”。肿瘤细胞中的糖酵解机制更为复杂，是多种因素综合调控的结果。异常的酶代谢是主要影响因素之一，抑制糖酵解的三个主要限速酶被认为是癌症治疗的重要策略。因此，近年来已经开发出许多糖酵解限速酶抑制剂，如最新的 HKII 抑制剂和 PKM2 抑制剂 Pachymic acid（PA）和 N-（4-（3-（3-（甲氨基）-3-氧代丙基）-5-（4'-（三氟甲基）-[1,1'-联苯]-4-基）-1H-吡唑-1-基）苯基）丙酰基）丙酰胺。本文综述了三种主要限速酶抑制剂的来源、构效关系、生物生态活性和作用机制，以期为限速酶抑制剂的设计和合成提供指导。
