| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
AZ505 targets SMYD2, a histone methyltransferase that methylates lysine residues on histone and non-histone proteins. SMYD2 is implicated in oncogenic signaling and fibrotic pathology. AZ505 is a potent and highly selective inhibitor of SMYD2 with an IC50 of 0.12 μM. It is a substrate competitive inhibitor, meaning it competes with the peptide substrate for binding to the enzyme. It displays >600-fold selectivity over SMYD3 (IC50 >83.3 μM), DOT1L (IC50 >83.3 μM), and EZH2 (IC50 >83.3 μM).
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| ln Vitro |
In vitro, AZ505 has submicromolar doses of action and is a highly selective drug. AZ505 has a greater IC50 (0.12) against SMYD2 than it does against other groups of methyltransferases (IC50>83.3 μM), DOT1L (IC50>83.3 μM), and EZH2 (IC50>83.3 μM) [1]. AZ505 has an IC50 of 0.12 μM, making it a powerful SMYD2 conjugate. There are five members of the human SMYD (SET and MYND domain-containing proteins) family of protein lysine transferases (SMYD1-5). Furthermore, protein lysine methyltransferase's enzymatic activity cannot be inhibited by AZ505. AZ505 with a Kd of 0.5 μM is assigned for ITC binding investigations. By contrast, the p53 substrate peptide's predicted Kd is 3.7 μM. The predominant entropy-driven binding of AZ505 to SMYD2 typically implies that binding is mediated by adjacency to a limited number of distinct hydrogen bonds [2].
In vitro, AZ505 inhibits SMYD2-mediated methylation with an IC50 of 0.12 μM. It is highly selective and shows activity at submicromolar concentrations. AZ505 has a greater IC50 (0.12 μM) against SMYD2 than it does against other groups of methyltransferases (IC50 >83.3 μM), DOT1L (IC50 >83.3 μM), and EZH2 (IC50 >83.3 μM). AZ505 fails to inhibit the enzymatic activities of a panel of protein lysine methyltransferases. The binding of AZ505 to SMYD2 is predominantly entropy-driven, suggesting that binding is mediated by adjacency to a limited number of distinct hydrogen bonds. |
| ln Vivo |
Specific in vivo data for AZ505 free base are not detailed in the available literature. However, the compound exhibits antiproliferative effects in preclinical cancer models. It is widely used as a research tool to investigate SMYD2 function, epigenetic regulation, and potential therapeutic strategies.
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| Enzyme Assay |
The enzymatic activity of AZ505 can be assessed using SMYD2 enzyme assays. Recombinant SMYD2 is incubated with a peptide substrate (e.g., p53 or histone H3) and the methyl donor S-adenosylmethionine (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. The binding affinity (Kd) can be measured using isothermal titration calorimetry (ITC).
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| Cell Assay |
To evaluate the cellular effects of AZ505, 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 AZ505 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 |
AZ505 free base has a molecular formula of C29H38Cl2N4O4 and a molecular weight of 577.54. Its CAS number is 1035227-43-0. The compound is an off-white to light brown solid powder. It has a logP of 5.412. The purity is ≥98%.
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| Toxicity/Toxicokinetics |
Specific toxicology data for AZ505 free base 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 |
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| Additional Infomation |
AZ505 is a benzoxazine compound with the structure 2H-1,4-benzoxazine-3(4H)-one, substituted with a hydroxyl group at position 5 and a 2-{[2-(cyclohexyl{N-[2-(3,4-dichlorophenyl)ethyl]-β-alanyl}amino)ethyl]amino}ethyl substitution at position 8. It is a potent and selective SMYD2 inhibitor. It functions as an EC 2.1.1.354 (histone H3-lysine(4)N-trimethyltransferase) inhibitor and an antitumor drug. It is a dichlorobenzene, tertiary amide, secondary amino compound, benzoxazine, and organic hydroxyl compound.
AZ505 free base is a potent and highly selective inhibitor of SMYD2 used as a research tool to study epigenetic regulation and cancer biology. It exhibits antiproliferative effects in preclinical cancer models. It is not a clinically approved drug. |
| Molecular Formula |
C29H38CL2N4O4
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|---|---|
| Molecular Weight |
577.542425632477
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| Exact Mass |
576.227
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| CAS # |
1035227-43-0
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| Related CAS # |
AZ505 ditrifluoroacetate;1035227-44-1
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| PubChem CID |
24961094
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| Appearance |
Off-white to light brown solid powder
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| LogP |
5.412
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
39
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| Complexity |
772
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LIBVHXXKHSODII-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H38Cl2N4O4/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)34-28/h6-9,18,22,32-33,36H,1-5,10-17,19H2,(H,34,37)
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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
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| Synonyms |
AZ-505 free base AZ-505 AZ505 AZ 505
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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 |
| 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 : ≥ 250 mg/mL (~432.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 6.25 mg/mL (10.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 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: 6.25 mg/mL (10.82 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 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: 6.25 mg/mL (10.82 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7315 mL | 8.6574 mL | 17.3148 mL | |
| 5 mM | 0.3463 mL | 1.7315 mL | 3.4630 mL | |
| 10 mM | 0.1731 mL | 0.8657 mL | 1.7315 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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