AZ505

AZ505 ditrifluoroacetate is a potent and highly selective inhibitor of the oncogenic protein SMYD2 (IC50=0.12 uM) with potential anticancer activity, >600 fold than SMYD3(IC50>83.3 uM); DOT1L(IC50>83.3 uM); EZH2(IC50>83.3 uM). The inhibition constant for AZ505 was determined to be 0.30 mM using Michaelis-Menten kinetics. A single AZ505 molecule is bound in the peptide binding groove of SMYD2. The cyclohexyl group of AZ505 is positioned in a primaryhydrophobic pocket that is formed at the interface of the core SET and I-SET domains, which is occupied by residue L369 of the p53 peptide. AZ505 has an IC50 value of 0.12 uM against SMYD2, and has no potency against SMYD3.