1,3,7-Trimethyluric Acid
(Synonyms: 1,3,7-三甲基尿酸,8-oxo Caffeine, NSC 11259) 目录号 : GC41837A metabolite of caffeine
Cas No.:5415-44-1
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
1,3,7-Trimethyluric acid is a methyl derivative of uric acid and a product of C-8 oxidation of caffeine by cytochrome P450 enzymes. It can be detected in urine as a marker of caffeine consumption.
Reference:
[1]. Tassaneeyakul, W., Birkett, D.J., McManus, M.E., et al. Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochem. Pharmacol. 47(10), 1767-1776 (1994).
[2]. Bhat, V.B., Sridhar, G.R., and Madyastha, K.M. Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-trimethyluric acid. Life Sci. 70(4), 381-393 (2001).
| Cas No. | 5415-44-1 | SDF | |
| 别名 | 1,3,7-三甲基尿酸,8-oxo Caffeine, NSC 11259 | ||
| 化学名 | 7,9-dihydro-1,3,7-trimethyl-1H-purine-2,6,8(3H)-trione | ||
| Canonical SMILES | O=C(N1)N(C)C2=C1N(C)C(N(C)C2=O)=O | ||
| 分子式 | C8H10N4O3 | 分子量 | 210.2 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 20 mg/ml,DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml | 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 | 4.7574 mL | 23.7869 mL | 47.5737 mL |
| 5 mM | 0.9515 mL | 4.7574 mL | 9.5147 mL |
| 10 mM | 0.4757 mL | 2.3787 mL | 4.7574 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。
Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-Trimethyluric Acid
Life Sci 2001 Dec 14;70(4):381-93.PMID:11798008DOI:10.1016/s0024-3205(01)01484-9.
New water-soluble analogues of 1,3,7-Trimethyluric Acid with N-1 methyl replaced by various groups were prepared and evaluated for their ability to scavenge hydroxyl radicals as well as their protective potential against lipid peroxidation in erythrocyte membranes. The deoxyribose degradation method indicates that all the analogues tested effectively scavenge hydroxyl radicals and some of them show better activity than uric acid and methyluric acids. These effects are shown to be concentration dependent and are more potent at low concentrations (10-50 microM). Among the analogues tested, 1-butenyl-, 1-propargyl- and 1-benzyl-3,7-dimethyluric acids show high hydroxyl radical scavenging property with a reaction rate constant (Ks) of 3.2-6.7 x 10(10) M(-1) S(-1), 2.3-3.7 x 10(10) M(-1) S(-1) and 2.4-3.7 x 10(10) M(-1) S(-1), respectively. The effectiveness of these analogues as hydroxyl radical scavengers appears to be better than mannitol (Ks, 1.9-2.5 x 10(9) M(-1) S(-1)). With the exception of 1-pentyl- and 1-(2'-oxopropyl)-3,7-dimethyluric acids, all other analogues tested are effective inhibitors of tert-butylhydroperoxide-induced lipid peroxidation in human erythrocyte membranes. All the analogues tested are susceptible to peroxidation in the presence of hemoprotein and hydrogen peroxide. The present study has pointed out that it is possible to significantly enhance the antioxidant property of 1,3,7-Trimethyluric Acid by structural modification at N-1 position. Such compounds may be useful as antioxidants in vivo.
Isotopic effects on retention times of caffeine and its metabolites 1,3,7-Trimethyluric Acid, theophylline, theobromine and paraxanthine
J Chromatogr B Biomed Sci Appl 1997 Jan 24;688(2):245-54.PMID:9061462DOI:10.1016/s0378-4347(96)00323-4.
Physicochemical parameters that influence gas chromatographic separation are numerous. Consequently, isotope labelling, because it modifies physicochemical properties, can induce isotopic effects on retention time. Caffeine has been chosen to study this influence because as itself and its metabolites, it allows the preparation of different methylxanthine isotopomers and thus is one of the best models to study isotopic effects induced by stable isotope labelling. Using a caffeine molecule labelled with deuterium at different positions and rat hepatocytes to obtain metabolites, it was possible to study the influence of labelling on retention time [(14% cyanopropylphenyl)methylpolysiloxane] and to point out the role of each labelled site. It appears that isotopic effects induced by the labelling depend not only on the number of labelling atoms but also on whether this labelling is at position 1, 3 or 7 and, consequently, on the role of the labelled site on the function of the molecule.
Role of Enzyme Flexibility in Ligand Access and Egress to Active Site: Bias-Exchange Metadynamics Study of 1,3,7-Trimethyluric Acid in Cytochrome P450 3A4
J Chem Theory Comput 2016 Apr 12;12(4):2101-9.PMID:26967371DOI:10.1021/acs.jctc.6b00075.
Although the majority of enzymes have buried active sites, very little is known about the energetics and mechanisms associated with substrate and product channeling in and out. Gaining direct information about these processes is a challenging task both for experimental and theoretical techniques. Here, we present a methodology that enables following of a ligand during its passage to the active site of cytochrome P450 (CYP) 3A4 and mapping of the free energy associated with this process. The technique is based on a combination of a bioinformatics tool for identifying access channels and bias-exchange metadynamics and provides converged free energies in good agreement with experimental data. In addition, it identifies the energetically preferred escape routes, limiting steps, and amino acids residues lining the channel. The approach was applied to mapping of a complex channel network in a complex environment, i.e., CYP3A4 attached to a lipid bilayer mimicking an endoplasmic reticulum membrane. The results provided direct information about the energetics and conformational changes associated with the ligand channeling. The methodology can easily be adapted to study channeling through other flexible biomacromolecular channels.
Strain differences in CYP3A-mediated C-8 hydroxylation (1,3,7-Trimethyluric Acid formation) of caffeine in Wistar and Dark Agouti rats. Rapid metabolism of caffeine in debrisoquine poor metabolizer model rats
Biochem Pharmacol 1998 May 1;55(9):1405-11.PMID:10076532DOI:10.1016/s0006-2952(97)00654-0.
We observed significant strain differences [Dark Agouti (DA) > Wistar] in 1,3,7-Trimethyluric Acid formation (C-8 hydroxylation) during caffeine metabolism, though not in N-demethylations, in adult male DA and Wistar rats. In contrast, adult female and immature male rats of both DA and Wistar strains did not show significant differences in activity levels of C-8 hydroxylation. Kinetic studies using liver microsomes revealed that adult male DA rats have a larger Vmax for C-8 hydroxylation than do Wistar rats. Troleandomycin (TAO), known as a cytochrome P450 (CYP) 3A inhibitor, and an anti-rat CYP3A2 polyclonal antibody effectively reduced C-8 hydroxylation by rat liver microsomes in a concentration-dependent manner, suggesting that C-8 hydroxylation in rats is mediated largely by an isoform(s) of the CYP3A subfamily. Troleandomycin and the antibody did not inhibit the N-demethylations of caffeine by rat liver microsomes. Treatment of rats with CYP3A inducers caused a marked increase in C-8 hydroxylase activity. These results indicate that the rat CYP3A subfamily is capable of catalyzing C-8 hydroxylation of caffeine as is the case for human CYP3A4. The results of western blotting analysis using anti CYP3A antiserum showed that the staining intensity of the protein band in DA rat liver microsomes was higher than that in Wistar rat liver microsomes. We concluded that marked sex-dependent strain differences in C-8 hydroxylation of caffeine between Wistar and DA rats are due to the differences in the levels of expression of CYP3A in these strains of rats.
Urine metabolomics signatures in reversible cerebral vasoconstriction syndrome
Cephalalgia 2020 Jun;40(7):735-747.PMID:31910660DOI:10.1177/0333102419897621.
Background: The pathophysiology of reversible cerebral vasoconstriction syndrome is unclear. An unbiased systems-based approach might help to illustrate the metabolite profiling and underlying pathophysiology. Methods: Urine samples were collected from reversible cerebral vasoconstriction syndrome patients and matched controls recruited in Taipei Veterans General Hospital. 1H-Nuclear magnetic resonance was used to initially explore the metabolic profile, and liquid chromatography tandem mass spectrometry was then used to identify metabolic alterations in reversible cerebral vasoconstriction syndrome. Untargeted metabolite screening was randomly performed on 10 reversible cerebral vasoconstriction syndrome patients and 10 control subjects in the discovery phase. The selected untargeted metabolites were further validated on 47 reversible cerebral vasoconstriction syndrome patients during their ictal stage (with 40 of them having remission samples) and 47 controls in the replication phase. Results and conclusion: Six metabolites-hippurate, citrate, 1,3,7-Trimethyluric Acid, ascorbic acid, D-glucurono-6,3-lactone, and D-threo-isocitric acid-with t-test derived p-value < 0.05 and VIP score >1, were identified as potential urine signatures that can well distinguish reversible cerebral vasoconstriction syndrome subjects at ictal stage from controls. Among them, citrate, hippurate, ascorbic acid, and D-glucurono-6,3-lactone were significantly lower, and 1,3,7-Trimethyluric Acid and D-threo-isocitric acid were higher in reversible cerebral vasoconstriction syndrome patients. Of these, four selected metabolites, citrate, D-glucurono-6,3-lactone, ascorbic acid, and 1,3,7-Trimethyluric Acid, returned to normal levels in remission. These metabolites are related to pathways associated with free radical scavenging, with the hub molecules being associated with endothelial dysfunction or sympathetic overactivity. Whether these metabolites and their implicated networks play a role in the pathogenesis of reversible cerebral vasoconstriction syndrome remains to be confirmed.