The methylation of lysine residues on histones plays a central role in determining euchromatin structure and gene expression. The histone methyltransferase (HMTase) G9a can mono- or dimethylate lysine 9 on histone 3 (H3), contributing to early embryogenesis, genomic imprinting, and lymphocyte development. UNC0321 is a potent and selective G9a HMTase inhibitor, exhibiting a Ki value of 63 pM. UNC0321 inhibits G9a with assay-dependent IC50 values of 6-9 nM and GLP, a closely-related H3K9 HMTase, with assay-dependent IC50 values of 15-23 nM. It is more than 40,000-fold selective against SET7/9 (a H3K4 HMTase), SET8 (a H4K20 HMTase), PRMT3, and JMJD2E.
