GSK126 is an indole-based inhibitor of EZH2 methyltransferase activity, with an Ki-app of 0.5-3 nM independent of substrate used. It is competitive with S-adenosyl methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against many other protein classes and methyltransferases, including both SET-domain-containing and non-SET-domain-containing classes. GSK126 decreases global H3K27me3 levels and reactivates silenced PRC2 target genes, as well as inhibits the proliferation of EZH2 mutant DLBCL cell lines and corresopnding xenografts in mice. The collection of pharmacological data suggests that GSK126 is a potential treatment for EZH2 mutant lymphoma. [1]

GSK126 is an indole-based inhibitor of EZH2 methyltransferase activity, with an Ki-app of 0.5-3 nM independent of substrate used. It is competitive with S-adenosyl methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against many other protein classes and methyltransferases, including both SET-domain-containing and non-SET-domain-containing classes. GSK126 decreases global H3K27me3 levels and reactivates silenced PRC2 target genes, as well as inhibits the proliferation of EZH2 mutant DLBCL cell lines and corresopnding xenografts in mice. The collection of pharmacological data suggests that GSK126 is a potential treatment for EZH2 mutant lymphoma. [1]