A-366

A-366 is a potent, highly selective inhibitor of histone methyltransferase G9a/GLP with IC50 of 3/38 nM, >1,000-fold selectivity for G9a over 21 other methyltransferases; effects a clear reduction in H3K9 methylation in cells, shows significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2 (H3K9me2 cellular EC50=0.3 uM) ; induces differentiation and affects viability in MV4;11 cells, demonstrates growth inhibition in vivo consistent with the profile of H3K9me2 reduction in flank xenograft leukemia model.