| 生化机理 |
EI1 demonstrated potent, concentration-dependent inhibition of the enzymatic activity against both Ezh2 wild-type and Y641F mutant enzymes with IC50 of 15 ± 2 nM and 13 ± 3 nM, respectively. Although SAM is the common cofactor for all HMTs, EI1 showed remarkable selectivity against Ezh2 over other HMTs. EI1 dramatically inhibited the H3K27me3 and H3K27me2 levels in these cells in a dose-dependent manner, but H3K27me1 was largely unchanged. The effect was similar in these cell lines, although they have different basal H3K27me3 and H3K27me2 levels. For example, in WSU-DLCL2, SU-DHL6, and Karpas422 with Ezh2 mutations, the H3K27me3 level was much higher than that in DLBCL cells with wild-type Ezh2 |
