GSK-503, a potent EZH2 inhibitor, has potential antitumor activity.

EZH2:8 nM

GSK503能够以相近的效力抑制WT和突变型EZH2的甲基转移酶活性。在七种DLBCL细胞系的研究中，GSK503显示出对细胞生长的抑制作用，并且这种效果在与ABT737或Obatoclax联用时得到增强。[1]

在接种SRBC的C57BL6小鼠中，GSK503（150 mg/kg，i.p.）降低了脾细胞中的H3K27me3水平。在携带SUDHL4和SUDHL6肿瘤的雄性SCID小鼠中，GSK503（150 mg/kg，i.p.）抑制了肿瘤生长。[1] 在携带鼠B16-F10肿瘤的C57Bl/6小鼠中，GSK503（150 mg/kg，i.p.）显著降低了全身H3K27me3水平，抑制了肿瘤生长，并几乎消除了转移形成。[2]

In vitro biochemical assays against histone acetylases: GSK503 is profiled to assess inhibition against a panel of histone acetylases. GSK503 is dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM, with a final DMSO concentration of 2%. Anacardic Acid is used as positive control for CBP, GCN5, and pCAF and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Curcumin is used as positive control for KAT5, MYST2/KAT7, MYST4/KAT6B, and p300, and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Reactions are carried out at 3.08 μM Acetyl-CoA. For CBP, GCN5, MYST2/KAT7, pCAF, and p300, the substrate used is histone H3. For KAT5 and MYST4/KAT6B the substrates used are histone H2A and histone H4, respectively.