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. UNC0224 is a potent and selective G9a HMTase inhibitor, exhibiting an IC50 value of 15 nM. Isothermal titration calorimetry revealed UNC0224 binds to G9a with a Kd value of 29 nM. UNC0224 also inhibits GLP, a closely-related H3K9 HMTase, with assay-dependent IC50 values of 20-58 nM, but is more than 1,000-fold selective against SET7/9 (a H3K4 HMTase) and SET8 (a H4K20 HMTase).
