GSK126

GSK126 is a cell permeable highly potent and selective small molecule inhibitor of histone methyltransferase EZH2, inhibiting potently both wild-type and mutant EZH2 methyltransferase activity with similar potencies (Kiapp =0.5-3 nM), independent of substrate used, and is competitive with S-adenosylmethionine (SAM) and noncompetitive with peptide substrates. It is 150-fold more selective for the closest EZH1 (Kiapp 89 nM) and more than 1, 000-fold selective over 20 other human methyltransferases, and multiple other protein classes, including both SET-domain-containing and non-SET domain-containing methyltransferases. It induced a 50% loss of H3K27me3 in both EZH2 wild type and mutant DLBCL cell lines at nM concentrations independent of EZH2 mutation status. GSK126 can decrease global H3K27me3 levels and reactivate silenced PRC2 target genes. It effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines, and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice.

Soluble in DMSO