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| Other Sizes |
| Targets |
DNA-dependent protein kinase (DNA-PK). DMNB is a DNA-dependent protein kinase (DNA-PK) inhibitor with an IC₅₀ of 15 μM. DNA-PK is a serine/threonine protein kinase that plays a critical role in the non-homologous end-joining (NHEJ) pathway of double-stranded DNA break repair in human cells. By inhibiting DNA-PK, DMNB prevents the repair of DNA double-strand breaks, which can lead to genomic instability and cell death. DMNB is a derivative of vanillin with 100-fold potency compared to vanillin. The compound's photolabile properties also enable its use as a caged proton donor for studying pH-dependent processes.
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| ln Vitro |
DMNB inhibits DNA-dependent protein kinase (DNA-PK) with an IC₅₀ of 15 μM. As a DNA-PK inhibitor, it blocks the non-homologous end-joining (NHEJ) pathway of double-stranded DNA break repair in human cells. The compound demonstrates 100-fold higher potency compared to vanillin. DMNB is shown in experiments to increase DR4/DR5 mRNA levels and their surface expression and decrease c-FLIP mRNA levels. DMNB also functions as a photolabile proton donor, releasing acid when excited at 405 nm, which has been used for fluorescence imaging studies of nuclear proton dynamics.
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| ln Vivo |
In vivo studies of DMNB are limited. As a DNA-PK inhibitor, it may have potential applications in cancer therapy, particularly in combination with DNA-damaging agents. The compound's photolabile properties suggest potential applications in photodynamic therapy or light-activated drug delivery. DMNB is used as a precursor for the synthesis of no-carrier-added 6-[¹⁸F]fluoro-L-DOPA (6-FDOPA) for PET studies of the dopaminergic system. Further studies are needed to characterize its in vivo pharmacokinetic and pharmacodynamic properties.
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| Enzyme Assay |
Non-cell-based assays for DMNB include DNA-PK kinase activity assays using purified DNA-PK enzyme. The enzyme is incubated with ATP and a peptide substrate in the presence of various concentrations of DMNB, and kinase activity is measured by the incorporation of radioactive phosphate or by using luminescent kinase assay kits. The IC₅₀ value of 15 μM is calculated from the dose-response curve. For photolabile proton donor characterization, the compound is irradiated at 405 nm and proton release is measured using pH-sensitive indicators. Standard analytical methods including HPLC, NMR, and mass spectrometry are used for compound characterization.
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| Cell Assay |
Cell-based assays for DMNB use human cell lines to assess DNA-PK inhibition and its effects on DNA repair. Cells are treated with DMNB at various concentrations, and DNA-PK activity is assessed by measuring the phosphorylation of DNA-PK substrates or by using reporter assays for NHEJ activity. DMNB has been shown to increase DR4/DR5 mRNA levels and their surface expression and decrease c-FLIP mRNA levels in cells. The compound's effects on DNA repair are assessed by exposing cells to DNA-damaging agents and measuring DNA repair kinetics using comet assays or γ-H2AX foci formation. Cytotoxicity is assessed using MTT or similar assays.
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| Animal Protocol |
In vivo studies of DMNB are limited. Potential animal models include tumor xenograft models for evaluating DNA-PK inhibition in combination with radiation or chemotherapy. For radiopharmaceutical applications, the compound is used as a precursor for the synthesis of 6-[¹⁸F]fluoro-L-DOPA for PET imaging. Biodistribution studies of 6-[¹⁸F]fluoro-L-DOPA have been conducted in normal and unilateral PD model rats. Standard protocols for these studies involve administration of the radiotracer followed by PET imaging or tissue analysis.
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| ADME/Pharmacokinetics |
DMNB has a molecular formula of C₉H₉NO₅ and a molecular weight of 211.17 g/mol. The melting point is 133.2-134.5°C. It appears as a light yellow to yellow solid powder. DMNB is insoluble in water but soluble in DMSO (100 mg/mL, 473.55 mM) and ethanol (25 mM with gentle warming). For in vivo formulation, it can be prepared in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline. The compound should be stored in a sealed and protected environment under nitrogen, avoiding exposure to moisture.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DMNB are limited. As a DNA-PK inhibitor, the compound may have genotoxic potential by interfering with DNA repair mechanisms. DNA-PK inhibitors can sensitize cells to DNA-damaging agents and may have off-target effects on normal tissues. The compound should be handled with appropriate safety precautions, including the use of personal protective equipment. It is intended for research use only and is not for human consumption. No carcinogenic or reproductive toxicity data are available.
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| References |
[1]. Zhang Lan, et al. Preparation of 6-[18F]fluoro-L-DOPA and its biodistribution in normal and unilateral PD model rats. Nuclear Science and Techniques, 13(4), 244-250.
[2]. Reddy GN, et al. Quality assurance and quality control methods for animal and human applications of no-carrier-added 6-[18F]fluorodopa for PET investigations of dopaminergic systems. Appl Radiat Isot. 1993;44(7):993-998. |
| Additional Infomation |
4,5-Dimethoxy-2-nitrobenzaldehyde is a C-nitro compound and an aromatic ether.
DMNB (6-Nitroveratraldehyde, 4,5-dimethoxy-2-nitrobenzaldehyde) is a multifunctional compound with applications in cancer research, chemical biology, and radiopharmaceutical synthesis. As a DNA-PK inhibitor with an IC₅₀ of 15 μM, it is used to study the NHEJ pathway of double-stranded DNA break repair. DNA-PK is an attractive target for cancer therapy, as its inhibition can sensitize tumor cells to radiation and chemotherapy. The compound also functions as a photolabile proton donor, releasing acid upon excitation at 405 nm, which has been used for fluorescence imaging studies. DMNB serves as a precursor for the synthesis of no-carrier-added 6-[¹⁸F]fluoro-L-DOPA, a radiopharmaceutical used in PET imaging for Parkinson's disease and other neurological disorders. It is for research use only. |
| Molecular Formula |
C9H9NO5
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|---|---|
| Molecular Weight |
211.17
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| Exact Mass |
211.048
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| CAS # |
20357-25-9
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| PubChem CID |
88505
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.312 g/cm3
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| Boiling Point |
390.8ºC at 760 mmHg
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| Melting Point |
133.2-134.5 °C
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| Flash Point |
194.3ºC
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| Vapour Pressure |
2.59E-06mmHg at 25°C
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| Index of Refraction |
1.571
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| LogP |
1.947
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
239
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1C([H])=C(C(C([H])=O)=C([H])C=1OC([H])([H])[H])[N+](=O)[O-]
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| InChi Key |
YWSPWKXREVSQCA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H9NO5/c1-14-8-3-6(5-11)7(10(12)13)4-9(8)15-2/h3-5H,1-2H3
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| Chemical Name |
4,5-dimethoxy-2-nitrobenzaldehyde
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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 (e.g. under nitrogen), 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: 100 mg/mL (473.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.84 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 25.0 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: 2.5 mg/mL (11.84 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7355 mL | 23.6776 mL | 47.3552 mL | |
| 5 mM | 0.9471 mL | 4.7355 mL | 9.4710 mL | |
| 10 mM | 0.4736 mL | 2.3678 mL | 4.7355 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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