1. Epigenetics
  2. Histone Methyltransferase

AZ505 

Cat. No.: HY-15226
Handling Instructions

AZ505 is a potent and selective SMYD2 inhibitor with IC50 of 0.12 μM.

For research use only. We do not sell to patients.
AZ505 Chemical Structure

AZ505 Chemical Structure

CAS No. : 1035227-43-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO $241 In-stock
5 mg $190 In-stock
10 mg $320 In-stock
25 mg $680 In-stock
50 mg $990 Get quote
100 mg $1500 Get quote
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of AZ505:

    AZ505 purchased from MCE. Usage Cited in: J Clin Invest. 2017 Jun 30;127(7):2751-2764.

    PKD-associated signaling pathways can be affected by SMYD2 in Pkd1 mutant renal epithelial cells and cystic tissues. Western blot analysis of the phosphorylation of ERK, S6, AKT, and Rb as well as the total protein levels of these proteins in Pkd1-null MEK cells with or without AZ505 treatment for 2 hours.
    • Biological Activity

    • Protocol

    • Technical Information

    • References

    Description

    AZ505 is a potent and selective SMYD2 inhibitor with IC50 of 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 IC50 of 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 IC50 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 Kd of 0.5 μM. In contrast, the calculated Kd 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[2].

    References
    Kinase Assay
    [2]

    SMYD2 is expressed in insect cells and purified. AlphaScreen technology is used to screen our chemical library for small molecule inhibitors of SMYD2. Methylation (12 μL) reactions are carried out in TDT buffer (50 mM Tris-HCl [pH 9.0], 2 mM DTT, and 0.01% Tween 20) at room temperature using 1.25 nM SMYD2 protein, 200 nM SAM, and 100 nM biotinylated p53 peptide substrate (Biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH) in low volume 384-well plates. Following a 75 min incubation period, reactions are quenched by the addition of 5 μL of detection solution (20 mM HEPES [pH 7.4], 1.7 mg/mL BSA, 340 mM NaCl, 680 μM SAH, 0.04 mg/mL Streptavidin-coated AlphaScreen donor, and Protein A-coated acceptor beads), and 1 nM of a custom p53K370me1 polyclonal antibody. Reaction plates are incubated overnight in the dark at room temperature, and read using an Envision 2101 Multi-label Reader. Compounds showing >50% inhibition of SMYD2 are nominated for concentration dose-response determination, and are also subjected to an artifact assay. Seven compound concentrations are selected beginning at 30 μM with six half-log dilution steps. The artifact assay conditions are identical to those in the SMYD2 enzymatic activity assay, except for the absence of SMYD2 protein and the presence of 1 nM methylated p53 peptide. IC50 values are calculated from dose-response data using in-house software[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

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    Product Name:
    AZ505
    Cat. No.:
    HY-15226
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