1-Methylxanthine
(Synonyms: 1-甲基黄嘌呤) 目录号 : GC60449
1-甲基黄嘌呤属于称为黄嘌呤的有机化合物类别。这些是嘌呤衍生物，在嘌呤部分的碳 2 和 6 处有一个酮基共轭。它也是由嘌呤核苷磷酸化酶从黄苷产生的。可增强肿瘤细胞的放射敏感性
Cas No.:6136-37-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
1-Methylxanthine is an active metabolite of caffeine .1,2 It enhances ionizing radiation-induced DNA double-strand break formation in RKO colorectal cancer cells when used at a concentration of 3 mM.1 1-Methylxanthine (100 ?M) inhibits the uptake of 6-carboxyfluorescein in CHO cells overexpressing human organic anion transporter 1 (OAT1).2 It has also been used as a biomarker of caffeine consumption.3
1.Youn, H., Kook, Y.H., Oh, E.-T., et al.1-Methylxanthine enhances the radiosensitivity of tumor cellsInt. J. Radiat. Biol.85(2)167-174(2009) 2.Rengelshausen, J., Lindenmaier, H., Cihlar, T., et al.Inhibition of the human organic anion transporter 1 by the caffeine metabolite 1-methylxanthineBiochem. Biophys. Res. Commun.320(1)90-94(2004) 3.González-Domínguez, R., Castellano-Escuder, P., Carmona, F., et al.Food and microbiota metabolites associate with cognitive decline in older subjects: A 12-year prospective studyMol. Nutr. Food Res.65(23)e2100606(2021)
| Cas No. | 6136-37-4 | SDF | |
| 别名 | 1-甲基黄嘌呤 | ||
| Canonical SMILES | O=C(N1C)NC2=C(N=CN2)C1=O | ||
| 分子式 | C6H6N4O2 | 分子量 | 166.14 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.019 mL | 30.0951 mL | 60.1902 mL |
| 5 mM | 1.2038 mL | 6.019 mL | 12.038 mL |
| 10 mM | 0.6019 mL | 3.0095 mL | 6.019 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
1-Methylxanthine enhances the radiosensitivity of tumor cells
Int J Radiat Biol 2009 Feb;85(2):167-74.PMID:19280470DOI:10.1080/09553000902741190.
Purpose: To determine the efficacy of a caffeine derivative 1-Methylxanthine (1-MTX) in increasing radiosensitivity of cancer cells and elucidate the underlying mechanisms in vitro. Materials and methods: RKO human colorectal cancer cells carrying wild type protein 53 kDa (p53) were incubated with 3 mM 1-MTX for 30 min, exposed to 4 Gy ionizing radiation, and further incubated with 1-MTX for three days. The clonogenic cell death was determined, and the cell cycle distribution and apoptosis were studied with flow cytometry at different times after irradiation. The DNA double strand break (DNA DSB) was examined using phosphorylated Histone2A (gamma-H2AX) foci formation, and the expression/activity of checkpoint 2 kinase (Chk2), cell division cycle 25 (Cdc25) phosphatase and cyclin B1/Cdc2 kinase were also investigated using western blotting and in vitro kinase assays. Results: The treatment with 3 mM 1-MTX increased the radiation-induced clonogenic and apoptotic cell death. The radiation-induced phosphorylation of Chk2 and Cdc25c and the radiation-induced increase in the cyclin B1/Cdc2 kinas activity were little affected by 1-MTX. The radiation-induced G2/M arrest was only slightly shortened and the expression of radiation-induced gamma-H2AX was markedly prolonged by 1-MTX. Conclusions: 1-MTX significantly increased the radiosensitivity of RKO human colorectal cancer cells carrying wild type p53 mainly by inhibiting the repair of radiation-induced DNA DSB without causing significant alteration in radiation-induced G2/M arrest. Such a radiosensitization occurred at 1-MTX concentrations almost non-toxic to the target tumor cells.
Demethylation of theophylline (1,3-dimethylxanthine) to 1-Methylxanthine: the first step of an antioxidising cascade
Redox Rep 2010;15(3):138-44.PMID:20594417DOI:10.1179/174329210X12650506623726.
The reaction of theophylline with HO(*) radical, produced by photolytic methods at pH 7, was studied in aqueous solution and the products characterised by HPLC and GC-MS. In addition to the expected 1,3-dimethyluric acid, the formation of 1-Methylxanthine and, to a lesser extent, of 3-methylxanthine was observed. Theoretical calculations confirmed the preferred formation of the former compound. Both demethylated products were also observed upon reaction of theophylline with O(*-) radical anion at pH approximately 13, and 1-Methylxanthine was consumed faster than 3-methylxanthine after its formation. Molecular oxygen had no significant effect on the formation of the mono-methylxanthine derivatives. A reaction mechanism for the demethylation of theophylline by oxidising radicals is proposed. This demethylation reaction can play an important role in the protection of biological targets against oxidative stress as the first step of an antioxidising cascade.
1-Methylxanthine derived from theophylline as an in vivo biochemical probe of allopurinol effect
Br J Clin Pharmacol 1991 Aug;32(2):238-41.PMID:1931474DOI:10.1111/j.1365-2125.1991.tb03888.x.
The urinary 1-methyluric acid (1MU) to 1-Methylxanthine (1MX) ratio has been assessed as a biochemical index of oxipurinol effect in vivo in man. Dosing with theophylline was used to produce 1MX as an intermediate metabolite in six healthy volunteers. A sigmoid Emax model was fitted to the data and gave a mean plasma oxipurinol IC50 of 3.0 +/- 1.1 mg l-1, a mean exponent n of 3.4 +/- 2.1 and a mean IC90 of 8.5 +/- 5.9 mg l-1. There was marked interindividual variability in the steepness of the plasma oxipurinol concentration response relationship, and in the plasma oxipurinol IC90 values. The study has confirmed the feasibility of using single doses of allopurinol to construct individual plasma oxipurinol concentration-response curves.
In vivo and in vitro 1-Methylxanthine metabolism in the rat. Evidence that the dehydrogenase form of xanthine oxidase predominates in intact perfused liver
Drug Metab Dispos 1987 May-Jun;15(3):295-9.PMID:2886302doi
Concentrations of 1-, 3-, and 7-methylxanthine and their uric acid metabolites were measured in plasma and brain affusate 20 min after ip injection of the monomethylxanthines into rats. 3-Methylxanthine was not metabolized to 3-methyluric acid. Similar concentrations of 7-methylxanthine and 7-methyluric acid were detected in both plasma and brain affusate. The oxidation of 1-Methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. Similar patterns in rates of metabolism (1-methyl- greater than 7-methyl- much greater than 3-methylxanthine) were observed in both intact animals and perfused rat liver. The metabolism of 1-Methylxanthine to 1-methyluric acid in perfused livers could be explained on the basis of the dehydrogenase form of xanthine oxidase. This conclusion is supported by the observations that the stoichiometry between oxygen utilization and methylurate formation was not consistent with catalysis by the oxidase form of the enzyme and that NADH formed from the metabolism of ethanol strongly inhibited 1-Methylxanthine oxidation. In perfused liver, anaerobic conditions decreased rates of 1-Methylxanthine metabolism by only 24%. These data demonstrate the presence of oxidizing substrates other than oxygen and NAD+ which are capable of maintaining xanthine oxidase activity during hypoxia. Moreover, rates of 1-Methylxanthine metabolism during anoxia could be restored to normal, aerobic values by the infusion of pyruvate, which increased hepatic levels of NAD+. These data demonstrate that changes in the hepatic oxidation-reduction state may dramatically affect rates of xanthine oxidase-dependent metabolism in intact cells.
1-Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect
Br J Clin Pharmacol 1997 Feb;43(2):197-200.PMID:9131954DOI:10.1046/j.1365-2125.1997.53711.x.
Aims: In the present study we have investigated the use of caffeine, administered in the form of instant coffee, as a prodrug for 1MX to validate the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase. Methods: Five healthy volunteers took caffeine 75 mg 8 hourly administered as instant coffee over a 7 day period. They were given allopurinol 600 mg on day 4. Urine was collected in 8 h aliquots from day 1-day 7. The ratio of 1-methyluric acid (1MU) to 1-methylxanthuric (1MX) was determined. Results: The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of each caffeine dosage interval and the decrement in the urinary 1MX to 1MU ratio fitted well by a sigmoid Emax model. Mean (+/-s.d.) values of the oxypurinol EC50(3.9 +/- 1.4 mg l-1), EC90(8.7 +/- 1.8 mgl-1) and the exponent, n (3.0 +/- 1.2) were similar to those obtained previously following either the direct administration of 1MX or the use of theophylline as a prodrug for 1MX. Conclusions: These data indicate that the use of caffeine as a source of 1MX could provide a simple and ethically acceptable method for monitoring oxypurinol effect in patients taking allopurinol for the treatment of gout.