AZ505 is a potent and highly selective inhibitor of the oncogenic protein SMYD2 (IC50=0.12 μM) with potential anticancer activity, > 600 fold than SMYD3 (IC50> 83.3 μM), DOT1L (IC50> 83.3 μM), EZH2 (IC50> 83.3 μM).
AZ505 is highly selective and shows an activity at submicromolar concentrations in vitro. The IC50 value of AZ505 against SMYD2 is 0.12 μM, representing a >600-fold difference compared to its IC50 values against other histone methyltransferases, such as SMYD3 (IC50>83.3 μM), DOT1L (IC50>83.3 μM), and EZH2 (IC50>83.3 μM) [1]. AZ505 functions as a potent and selective inhibitor of SMYD2, with an IC50 of 0.12 μM. The human SMYD (SET and MYND domain-containing protein) family comprises five members (SMYD1-5). Additionally, AZ505 does not inhibit the enzymatic activities of a range of protein lysine methyltransferases. AZ505 has been proposed for an isothermal titration calorimetry (ITC) binding study, with a Kd value of 0.5 μM. Conversely, the calculated Kd for the p53 substrate peptide is 3.7 μM. The interaction between AZ505 and SMYD2 is primarily governed by entropy, implying that binding is predominantly facilitated by hydrophobic interactions with minimal specific hydrogen bonding [2].
作用机制
AZ505 is a substrate competitive inhibitor which can bound in the peptide binding groove of SMYD2.[1]
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