Six years (2012-2018) of researches on catalytic EZH2 inhibitors: the boom of the 2-pyridone compounds
Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), catalyzes the methylation of lysine 27 of histone H3 (H3K27) up to its trimethylated form (H3K27me), inducing by this way block of transcription and gene silencing. High levels of H3K27me3 have been found in both hematological malignancies and solid cancers, due to EZH2 overexpression and/or EZH2 mutation. From 2012, a number of highly potent and selective catalytic inhibitors of EZH2 have been reported, almost all bearing a 2-pyridone group in their structure.