a-366

A-366 is a potent, highly selective, peptide-competitive small molecule inhibitor of the histone lysine methyltransferases G9a (EHMT2) and GLP (EHMT1), with IC50 values of 3.3 nM and 38 nM, respectively. It demonstrates >100-fold selectivity for G9a/GLP over other methyltransferases and non-epigenetic targets. A-366 reduces the dimethylation of lysine 9 on histone H3 (H3K9me2) in cells, acting as an epigenetic modulator. The compound also exhibits direct binding to the Tudor domain of Spindlin-1 (SPIN1), though cellular activity for this target occurs at higher concentrations. A-366 is primarily used as a research tool to probe the biological functions of G9a/GLP and related epigenetic pathways in cancer and stem cell biology. It is not approved as a therapeutic agent[1][2][3][4][6][7][8].