| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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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