"目录号: HY-15226
Epigenetics-
AZ505 是一种有效的，具有选择性的SMYD2抑制剂，IC50值为 0.12 μM。
Histone Methyltransferase
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生物活性
Description
AZ505 is a potent and selectiveSMYD2inhibitor withIC50of 0.12 μM.
IC50& Target
IC50: 0.12 μM (SMYD2)[1]
In Vitro
AZ505 is highly selective and shows an activity at submicromolar concentrations in vitro. The IC50of AZ505 for SMYD2 is 0.12 μM, which is >600-fold greater than the IC50s of AZ505 for other histone methyltransferases, such as SMYD3 (IC50>83.3 μM), DOT1L (IC50>83.3 μM) and EZH2 (IC50>83.3 μM)[1]. AZ505 is a potent and selective SMYD2 inhibitor with an IC50of 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 Kdof 0.5 μM. In contrast, the calculated Kdfor 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[2].
References
[1].Komatsu S, et al. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. Br J Cancer. 2015 Jan 20;112(2):357-64.
[2].Ferguson AD, et al. Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73.
[3].Li LX, et al. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 2017 Jun 30;127(7):2751-2764.