A novel inhibitor of PGK1 suppresses the aerobic glycolysis and proliferation of hepatocellular carcinoma

Phosphoglycerate kinase 1(PGK1) is an important enzyme in the metabolic glycolysis pathway. Nowadays, PGK1 is an appealing therapeutic target for multiple cancers. However, no effective inhibitor of PGK1 has been reported. In this study, we demonstrate that Ilicicolin H a 5-(4-hydroxyphenyl)-pyridone with a decalin ring system and a non-ATP-competitive inhibitor of PGK1, inhibits the proliferation and promotes apoptosis of Hepatocellular carcinoma (HCC). Many cancer cells display enhanced glycolysis which is critical for tumor development. Here we identified that Ilicicolin H can target PGK1 in vitro to inhibit the lactate production and glucose uptake of HCC cells. These findings suggest that the PGK1 inhibitor- Ilicicolin H is a promising anticancer agent and may provide a better therapeutic strategy for HCC treatment in the future.