Biological Activity
az505 is a potent set and mynd domain-containing 2 protein (smyd2) inhibitor that selectively inhibits the enzymatic activity of smyd2 (ic50: 0.12 μm) over a variety of other protein lysine methyltransferases (ic50 > 83.3 μμ), including smyd3, dot1l, ezh2, glp, g9a and set7/9 [1].az505 contains three distinct moieties: the benzooxazinone group which interacts with the lysine-binding channel of smyd2; the cyclohexyl group which interacts with the core set and i-set domains of smyd2; and the dichlorophenethyl group which extends across the peptide binding groove of smyd2 [1].the x-ray crystallographic analysis has revealed that az505 binds into the peptide binding groove of smyd2 competing with the peptide substrates [1].
