N-环己基-3-(3,4-二氯苯乙基氨基)-N-[2-[[2-[5-羟基-3-氧代-3,4-二氢-2H-苯并[B][1,4]恶嗪-8-基]乙基]氨基]乙基]丙酰胺

IC50: 0.12 μM (SMYD2)

AZ505 is highly selective and shows an activity at submicromolar concentrations in vitro. The IC ₅₀ of AZ505 for SMYD2 is 0.12 μM, which is >600-fold greater than the IC ₅₀ s of AZ505 for other histone methyltransferases, such as SMYD3 (IC ₅₀ >83.3 μM), DOT1L (IC ₅₀ >83.3 μM) and EZH2 (IC ₅₀ >83.3 μM). AZ505 is a potent and selective SMYD2 inhibitor with an IC ₅₀ of 0.12 μM. The human SMYD (SET and MYND domain-containing protein) family of protein lysine methyltransferases contains five members (SMYD1-5). Moreover, AZ505 fails to inhibit the enzymatic activities of a panel of protein lysine methyltransferases. AZ505 is nominated for ITC binding study with K _d of 0.5 μM. In contrast, the calculated K _d for the p53 substrate peptide is 3.7 μM. AZ505 binding to SMYD2 is driven primarily by entropy, which often suggests that binding is mediated by hydrophobic interactions with few specific hydrogen bonds.