| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary molecular target of 6-O-Methyldeoxyguanosine is the DNA itself, where it acts as a damaged base. In a biological context, it is recognized by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). MGMT transfers the methyl group from the O6 position of guanine to a cysteine residue in its own active site, thereby repairing the lesion. Unrepaired, this adduct mispairs with thymine during DNA replication.
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| ln Vitro |
In vitro, 6-O-Methyldeoxyguanosine is a standard substrate for studying MGMT activity and DNA repair. It is used to quantify the activity of MGMT in cell extracts by measuring the transfer of the tritiated methyl group from the DNA adduct to the MGMT protein. It is also used in primer extension assays to demonstrate how DNA polymerases bypass this lesion, leading to misincorporation of thymine instead of cytosine.
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| ln Vivo |
In vivo, 6-O-Methyldeoxyguanosine is the primary cytotoxic/cytostatic lesion formed by DNA alkylating agents used in chemotherapy, such as temozolomide (TMZ), which is a standard treatment for glioblastoma. The level of this adduct in tumors is directly correlated with the efficacy of TMZ, making it a key biomarker. Tumors with low MGMT expression (which cannot repair this lesion) are more sensitive to treatment.
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| Enzyme Assay |
A cell-free assay for MGMT activity uses DNA containing 6-O-[3H]methyldeoxyguanosine. Cell extract or purified MGMT is incubated with the radiolabeled DNA. The reaction is terminated by adding protein precipitation solution. The amount of tritium transferred to the MGMT protein is measured by liquid scintillation counting after separating the protein from the DNA. This directly measures the repair activity.
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| Cell Assay |
For cellular studies, cancer cells (e.g., glioblastoma cell lines) are treated with an alkylating agent like temozolomide. Cells are harvested, and DNA is isolated. The levels of 6-O-Methyldeoxyguanosine are measured to assess DNA damage. Alternatively, MGMT activity is quantified by incubating cell lysates with a DNA substrate containing 6-O-[3H]methyldeoxyguanosine and measuring the transfer of the radiolabel to the MGMT protein.
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| Animal Protocol |
For in vivo studies, mice bearing subcutaneous tumor xenografts (e.g., glioblastoma) are treated with temozolomide or an investigational alkylator. After treatment, tumors are excised, and DNA is isolated. The levels of 6-O-Methyldeoxyguanosine can be quantified by LC-MS/MS or by a radioimmunoassay to correlate adduct formation with antitumor activity. This is crucial for pharmacodynamic assessments of alkylating agents.
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| ADME/Pharmacokinetics |
As a modified nucleoside, 6-O-Methyldeoxyguanosine itself is not a drug; therefore, its ADME properties are not relevant. When formed in vivo as a DNA adduct, its half-life depends on the rate of repair by MGMT and the rate of cell division. In the absence of MGMT (e.g., in MGMT-methylated tumors), the adduct is persistent and its accumulation drives the cytotoxic effect of alkylating chemotherapy.
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| Toxicity/Toxicokinetics |
6-O-Methyldeoxyguanosine is not a therapeutic agent but a highly toxic DNA lesion. When formed in DNA, it is cytotoxic and mutagenic. Its toxicity is the basis for the efficacy of alkylating chemotherapy. Tumors deficient in MGMT are sensitive to this toxicity. The toxicology is not of the compound itself but of the lesion it represents. Understanding its formation and repair is crucial for mitigating chemotherapy resistance.
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| References | |
| Additional Infomation |
O(6)-methyl-2'-deoxyguanosine is a purine 2'-deoxyribonucleoside with the nucleobase O(6)-methylguanine. It is functionally related to guanine.
6-O-Methyldeoxyguanosine is the canonical mutagenic DNA adduct caused by alkylating agents, including those found in cigarette smoke and industrial chemicals. It is a critical biomarker for assessing exposure to environmental mutagens. In cancer chemotherapy, the activity of the DNA repair protein MGMT is a major predictor of patient response to temozolomide. This adduct is central to the pharmacology of alkylating agents used to treat brain tumors. It is used as a research compound to study mechanisms of chemoresistance. Searched |
| Molecular Formula |
C11H15N5O4
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|---|---|
| Molecular Weight |
281.27
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| Exact Mass |
281.112
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| CAS # |
964-21-6
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| PubChem CID |
73317
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| Appearance |
White to off-white solid powder
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| Density |
1.84 g/cm3
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| Boiling Point |
674.7ºC at 760 mmHg
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| Flash Point |
361.9ºC
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| Index of Refraction |
1.794
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| LogP |
0.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
349
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| Defined Atom Stereocenter Count |
3
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| SMILES |
COC1=NC(=NC2=C1N=CN2[C@H]3C[C@@H]([C@H](O3)CO)O)N
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| InChi Key |
BCKDNMPYCIOBTA-RRKCRQDMSA-N
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| InChi Code |
InChI=1S/C11H15N5O4/c1-19-10-8-9(14-11(12)15-10)16(4-13-8)7-2-5(18)6(3-17)20-7/h4-7,17-18H,2-3H2,1H3,(H2,12,14,15)/t5-,6+,7+/m0/s1
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| Chemical Name |
(2R,3S,5R)-5-(2-amino-6-methoxypurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~355.5 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (8.89 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5553 mL | 17.7765 mL | 35.5530 mL | |
| 5 mM | 0.7111 mL | 3.5553 mL | 7.1106 mL | |
| 10 mM | 0.3555 mL | 1.7777 mL | 3.5553 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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