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Methionine cycle and mode of action of several EZH2 inhibitors. DNZep is an inhibitor of SAH hydrolase leading to an accumulation of SAH which in turn inhibits EZH2 activity, as well as other cellular methltransferases. SAM competitors such as EPZ005687, EPZ-6438, EI1, UNC1999 and GSK126 bind to the SAH-binding pocket of EZH2 to prevent the recruitment of the SAM methyl donor. SAH-EZH2 peptides disrupt the PRC2 assembly required for full EZH2 activity.
