AZ505 ditrifluoroacetate is an effective and selective SMYD2 inhibitor (IC50: 0.12 μM).

SMYD2:0.12 μM

AZ505 ditrifluoroacetate is highly selective and shows activity at submicromolar concentrations in vitro. The IC50 of AZ505 ditrifluoroacetate for SMYD2 is 0.12 μM, which is >600-fold greater than the IC50s for other histone methyltransferases, such as SMYD3 (IC50>83.3 μM), DOT1L (IC50>83.3 μM) [1]. AZ505 ditrifluoroacetate is nominated for ITC binding study (Kd: 0.5 μM). In contrast, the calculated Kd for the p53 substrate peptide is 3.7 μM. AZ505 ditrifluoroacetate binding to SMYD2 is driven primarily by entropy, which often suggests that binding is mediated by hydrophobic interactions with few specific hydrogen bonds [2].