New natural inhibitors of hexokinase 2 (HK2): Steroids from Ganoderma sinense

A total of 13 steroids (1-13) including two new ones (1-2) were isolated from the fruiting bodies of Ganoderma sinense. Among them, (22E,24R)-6β-methoxyergosta-7,9(11),22-triene-3β,5α-diol (2) was found to have the highest binding affinity to HK2. In vitro MST, enzyme inhibition, and cell-based assays were undertaken to identify compound 2 as a HK2 inhibitor using this method. In vitro MST, enzyme inhibition and cell-based assays further validated compound 2 as a potential HK2 inhibitor.122