| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
AZ-505 2TFA salt targets SMYD2, a protein lysine methyltransferase implicated in oncogenic signaling. The compound inhibits SMYD2 with an IC50 of 0.12 μM. It is over 600-fold more selective for SMYD2 than for other histone methyltransferases such as SMYD3 (IC50 >83.3 μM), DOT1L (IC50 >83.3 μM), EZH2 (IC50 >83.3 μM), GLP, G9A, and SET7/9. SMYD2 plays a crucial role in tumor cell proliferation through its overexpression.
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| ln Vitro |
In vitro, AZ505 ditrifluoroacetate has activity at submicromolar doses and is a highly selective drug. When it comes to other histone methyltransferases like DOT1L (IC50>83.3 μM), SMYD3 (IC50>83.3 μM), and AZ505 Ditrifluoroacetate, the latter has an IC50 more than 600 times higher than that of SMYD2. The IC50 of AZ505 ditrifluoroacetate against SMYD2 is 0.12 μM. IC50 greater than 83.3 μM)[1]. With an IC50 of 0.12 μM, AZ505 ditrifluacetate is a strong and specific SMYD2 inhibitor. There are five members of the human lysine methyltransferase family known as SMYD (SET and MYND domain-containing protein) (SMYD1-5). Moreover, AZ505 ditrifluoroacetate failed to stop a set of protein lysine methyltransferases from doing their job. With a Kd of 0.5 μM, AZ505 ditrifluoroacetate was proposed for ITC binding investigations. By contrast, the p53 substrate peptide's predicted Kd is 3.7 μM. The primary mechanism of AZ505 ditrifluoroacetate's binding to SMYD2 is entropy, which generally implies that hydrophobic interactions with a small number of particular hydrogen bonds mediate the binding [2].
In vitro, AZ-505 2TFA salt inhibits SMYD2-mediated methylation with an IC50 of 0.12 μM. It is highly selective and shows activity at submicromolar concentrations. The compound has an IC50 of 0.12 μM against SMYD2, which is over 600-fold lower than its IC50 for other histone methyltransferases such as SMYD3 (IC50 >83.3 μM) and DOT1L (IC50 >83.3 μM). |
| ln Vivo |
Specific in vivo data for AZ-505 2TFA salt are not detailed in the available literature. However, as a potent and selective SMYD2 inhibitor, it is expected to have anticancer activity. It could be used in preclinical studies to investigate the role of SMYD2 in cancer and other diseases.
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| Enzyme Assay |
The enzymatic activity of AZ-505 2TFA salt can be assessed using SMYD2 enzyme assays. Recombinant SMYD2 is incubated with a peptide substrate and SAM in the presence of varying concentrations of the inhibitor. The extent of methylation is measured using techniques such as radioactive labeling or mass spectrometry. The IC50 value for SMYD2 inhibition is determined from dose-response curves.
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| Cell Assay |
To evaluate the cellular effects of AZ-505 2TFA salt, cells are treated with the compound, and the methylation of SMYD2 substrates is measured by Western blotting using methylation-specific antibodies. Cell proliferation and viability are assessed using standard assays. The compound's effects on gene expression and downstream signaling pathways can also be evaluated.
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| Animal Protocol |
In vivo studies with AZ-505 2TFA salt would typically involve administration to tumor-bearing mice in xenograft models. The compound's effects on tumor growth, SMYD2 substrate methylation, and other biomarkers would be measured. Pharmacokinetic parameters would also be characterized.
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| ADME/Pharmacokinetics |
AZ-505 2TFA salt has a molecular weight of 577.54 (free base) plus the mass of two trifluoroacetate groups. Its CAS number is 1035227-44-1. The compound is a ditrifluoroacetate salt. It is soluble in DMSO and other organic solvents. The purity is typically ≥98%.
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| Toxicity/Toxicokinetics |
Specific toxicology data for AZ-505 2TFA salt are not detailed in the available literature. However, its selectivity for SMYD2 over other methyltransferases suggests a potentially lower risk of off-target toxicity. As with all research compounds, standard safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
AZ-505 2TFA salt is a potent and highly selective inhibitor of SMYD2 used as a research tool to study epigenetic regulation and cancer biology. It has anticancer activity and is used to investigate the role of SMYD2 in tumor cell proliferation. It is not a clinically approved drug.
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| Molecular Formula |
C29H38CL2N4O4
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|---|---|
| Molecular Weight |
805.5891
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| Exact Mass |
804.212
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| CAS # |
1035227-44-1
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| Related CAS # |
AZ505;1035227-43-0
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| PubChem CID |
78357790
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| Appearance |
White to light yellow solid powder
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| LogP |
5.412
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
53
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| Complexity |
855
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LTZSXVZCRINTGV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H38Cl2N4O4.2C2HF3O2/c30-23-8-6-20(18-24(23)31)10-13-32-15-12-27(38)35(22-4-2-1-3-5-22)17-16-33-14-11-21-7-9-25(36)28-29(21)39-19-26(37)34-282*3-2(4,5)1(6)7/h6-9,18,22,32-33,36H,1-5,10-17,19H2,(H,34,37)2*(H,6,7)
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| Chemical Name |
N-cyclohexyl-3-((3,4-dichlorophenethyl)amino)-N-(2-((2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)amino)ethyl)propanamide
bis(2,2,2-trifluoroacetate)
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| Synonyms |
AZ505 ditrifluoroacetate salt AZ 505 2TFA salt AZ-505 2TFA salt
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 125 mg/mL (~155.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (2.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2413 mL | 6.2066 mL | 12.4133 mL | |
| 5 mM | 0.2483 mL | 1.2413 mL | 2.4827 mL | |
| 10 mM | 0.1241 mL | 0.6207 mL | 1.2413 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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