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Histone methyltransferase inhibitors target the enzymes that methylate lysine residues on histone tails. Lysine methyltransferases transfer methyl groups from S-adenosylmethionine to defined lysines, most often on histone H3. Methylation of lysine 27 of histone H3 (H3K27) by enhancer of zeste homolog 2 (EZH2) is linked to Polycomb gene silencing, while H3K9 methylation marks heterochromatin. Most compounds here target EZH2, including GSK126, GSK343 and tazemetostat, which compete with S-adenosylmethionine. UNC0642 inhibits G9a and G9a-like protein (GLP), pinometostat targets the H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L), and chaetocin acts on suppressor of variegation 3-9 homolog (SUV39H) enzymes. Inhibitors of arginine-directed enzymes are listed under Protein Arginine Methyltransferases.
