变构调节
化学
糖酵解
磷酸果糖激酶2
激活剂(遗传学)
酶
癌细胞
生物化学
磷酸果糖激酶
激酶
瓦博格效应
2,6-二磷酸果糖
癌症
生物
受体
遗传学
作者
Yinhu Wang,Chen Qu,Tingting Liu,Chunhui Wang
标识
DOI:10.1016/j.ejmech.2020.112612
摘要
Cancer cells adopt aerobic glycolysis as the major source of energy and biomass production for fast cell proliferation. The bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), plays a crucial role in the regulation of glycolysis by controlling the steady-state cytoplasmic levels of fructose-2,6-bisphosphate (F2,6BP), which is the most potent allosteric activator of 6-phosphofructo-1-kinase (PFK-1), a key rate-limiting enzyme of glycolysis. Therefore, selective inhibition of PFKFB3 has gained substantial interest as an attractive strategy for cancer therapy. In recent years, numerous class PFKFB3 inhibitors have been disclosed, and emerging trends such as the availability of PFKFB3 crystal structures, structure-based screening strategies and diverse functional assays are improving optimization and development of original leads. Herein, we review the structure and function of PFKFB3 as well as the representative small-molecule inhibitors, in particular emphasis on their chemical structures, pharmacological properties, selectivity, binding modes and structure-activity relationships (SARs).
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