The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (
3) and GSK343 (
6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
Keywords:
Epigenetics; EZH2; H3K27me3; methyltransferase; PRC2; SAM-competitive inhibitor