5,6-Dihydrouracil
(Synonyms: 二氢尿嘧啶; 5,6-Dihydrouracil) 目录号 : GC33650
A catabolite of uracil
Cas No.:504-07-4
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
5,6-Dihydrouracil is a catabolite of uracil .1 It is formed from uracil by dihydropyrimidine dehydrogenase. The plasma ratio of 5,6-dihydrouracil to uracil has been used as a phenotypic marker of dihydropyrimidine dehydrogenase activity.2
1.Büchel, B., Rhyn, P., Schürch, S., et al.LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patientsBiomed. Chromatogr.27(1)7-16(2013) 2.Chavani, O., Jensen, B.P., Strother, R.M., et al.Development, validation and application of a novel liquid chromatography tandem mass spectrometry assay measuring uracil, 5,6-dihydrouracil, 5-fluorouracil, 5,6-dihydro-5-fluorouracil, α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine in human plasmaJ. Pharm. Biomed. Anal.142125-135(2017)
| Cas No. | 504-07-4 | SDF | |
| 别名 | 二氢尿嘧啶; 5,6-Dihydrouracil | ||
| Canonical SMILES | O=C1CCNC(N1)=O | ||
| 分子式 | C4H6N2O2 | 分子量 | 114.1 |
| 溶解度 | DMSO : 14.29 mg/mL (125.24 mM; Need ultrasonic); H2O : 6.67 mg/mL (58.46 mM; ultrasonic and warming and heat to 60°C) | 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 | 8.7642 mL | 43.8212 mL | 87.6424 mL |
| 5 mM | 1.7528 mL | 8.7642 mL | 17.5285 mL |
| 10 mM | 0.8764 mL | 4.3821 mL | 8.7642 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。
(R)-5-fluoro-5,6-dihydrouracil: kinetics of oxidation by dihydropyrimidine dehydrogenase and hydrolysis by dihydropyrimidine aminohydrolase
Biochem Pharmacol 1994 Aug 17;48(4):775-9.PMID:8080451DOI:10.1016/0006-2952(94)90056-6.
The biologically active isomer of 5-fluoro-5,6-dihydrouracil [(R)-5-fluoro-5,6-dihydrouracil, R-FUH2] was synthesized to study the kinetics of its enzymatic oxidation and hydrolysis by homogeneous dihydropyrimidine dehydrogenase (DPDase) and dihydropyrimidine aminohydrolase (DPHase), respectively. DPDase catalyzed the slow oxidation of R-FUH2 at pH 8 and 37 degrees with a Km of 210 microM and a kcat of 0.026 sec-1 at a saturating concentration of NADP+. The catalytic efficiency (kcat/Km) of DPDase for R-FUH2 was 1/14th of that for 5,6-Dihydrouracil (UH2). In the opposite direction, DPDase catalyzed the reduction of 5-fluorouracil (FU) with a Km of 0.70 microM and a kcat of 3 sec-1 at a saturating concentration of NADPH. Thus, DPDase catalyzed the reduction of FU 30,000-fold more efficiently than the oxidation of R-FUH2. In contrast to the slow oxidation of R-FUH2 by DPDase, R-FUH2 was hydrolyzed very efficiently by DPHase with a Km of 130 microM and a kcat of 126 sec-1. The catalytic efficiency of DPHase for the hydrolysis of R-FUH2 was approximately twice that for the hydrolysis of UH2. Because R-FUH2 is hydrolysis of R-FUH2 was approximately twice that for the hydrolysis of UH2. Because R-FUH2 is hydrolyzed considerably more efficiently than it is oxidized and because the activity of DPHase was 250- to 500-fold greater than that of DPDase in bovine and rat liver, the hydrolytic pathway should predominate in vivo.
LC-MS/MS method for simultaneous analysis of uracil, 5,6-Dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients
Biomed Chromatogr 2013 Jan;27(1):7-16.PMID:22454320DOI:10.1002/bmc.2741.
The chemotherapeutic drug 5-fluorouracil (5-FU) is widely used for treating solid tumors. Response to 5-FU treatment is variable with 10-30% of patients experiencing serious toxicity partly explained by reduced activity of dihydropyrimidine dehydrogenase (DPD). DPD converts endogenous uracil (U) into 5,6-Dihydrouracil (UH(2) ), and analogously, 5-FU into 5-fluoro-5,6-dihydrouracil (5-FUH(2) ). Combined quantification of U and UH(2) with 5-FU and 5-FUH(2) may provide a pre-therapeutic assessment of DPD activity and further guide drug dosing during therapy. Here, we report the development of a liquid chromatography-tandem mass spectrometry assay for simultaneous quantification of U, UH(2) , 5-FU and 5-FUH(2) in human plasma. Samples were prepared by liquid-liquid extraction with 10:1 ethyl acetate-2-propanol (v/v). The evaporated samples were reconstituted in 0.1% formic acid and 10 μL aliquots were injected into the HPLC system. Analyte separation was achieved on an Atlantis dC(18) column with a mobile phase consisting of 1.0 mm ammonium acetate, 0.5 mm formic acid and 3.3% methanol. Positively ionized analytes were detected by multiple reaction monitoring. The analytical response was linear in the range 0.01-10 μm for U, 0.1-10 μm for UH(2) , 0.1-75 μm for 5-FU and 0.75-75 μm for 5-FUH(2) , covering the expected concentration ranges in plasma. The method was validated following the FDA guidelines and applied to clinical samples obtained from ten 5-FU-treated colorectal cancer patients. The present method merges the analysis of 5-FU pharmacokinetics and DPD activity into a single assay representing a valuable tool to improve the efficacy and safety of 5-FU-based chemotherapy.
Predicting 5-fluorouracil toxicity: DPD genotype and 5,6-Dihydrouracil:uracil ratio
Pharmacogenomics 2014 Sep;15(13):1653-66.PMID:25410891DOI:10.2217/pgs.14.126.
Aim: Decreased DPD activity is a major cause of 5-fluorouracil (5-FU) toxicity, but known reduced-function variants in the DPD gene (DPYD) explain only a part of DPD-related 5-FU toxicities. Here, we evaluated the baseline (pretherapeutic) plasma 5,6-Dihydrouracil:uracil (UH2:U) ratio as a marker of DPD activity in the context of DPYD genotypes. Materials & methods: DPYD variants were genotyped and plasma U, UH2 and 5-FU concentrations were determined by liquid chromatography-tandem mass spectrometry in 320 healthy blood donors and 28 cancer patients receiving 5-FU-based chemotherapy. Results: Baseline UH2:U ratios were strongly correlated with generally low and highly variable U concentrations. Reduced-function DPYD variants were only weakly associated with lower baseline UH2:U ratios. However, the interindividual variability in the UH2:U ratio was reduced and a stronger correlation between ratios and 5-FU exposure was observed in cancer patients during 5-FU administration. Conclusion: These results suggest that the baseline UH2:U plasma ratio in most individuals reflects the nonsaturated state of DPD and is not predictive of decreased DPD activity. It may, however, be highly predictive at increased substrate concentrations, as observed during 5-FU administration.
Role of enzymatically catalyzed 5-iodo-5,6-dihydrouracil ring hydrolysis on the dehalogenation of 5-iodouracil
J Biol Chem 1976 Nov 25;251(22):6909-14.PMID:993199doi
Incubation of 5-iodo-5,6-dihydrouracil (IH2Ura) with soluble rat liver enzymes at 37 degrees, pH 8.2, results in the rapid release of iodide ion. The second product resulting from the carbon skeleton of the dihydropyrimidine ring system is 2-amino-2-oxazoline-5-carboxylic acid (I). Ultraviolet absorbance measurements at 225 nm, where both IH2Ura and iodide ion absorb, indicate that IH2Ura dehalogenation is a two-step process. The first step, which is enzyme-dependent, involves dihydropyrimidine amidohydrolase (EC 3.5.2.2.)-catalyzed hydrolysis of the IH2Ura ring system presumably to yield 2-iodo-3-ureidopropionate. The enzyme preparations also catalyze the hydrolysis of 5-bromo-5,6-dihydrouracil, 5,6-Dihydrouracil, and 5,6-dihydrothymine, the latter two of which are the natural substrates for dihydropyrimidine amidohydrolase. The second step in IH2Ura dehalogenation involves the nonenzymatically catalyzed, pH-independent intramolecular cyclization of 2-iodo-3-ureidopropionate via nucleophilic attack of the ureido oxygen atom on carbon-2 resulting in iodide ion and the oxazoline (I) as final products. The results are discussed relative to the role of pyrimidine catabolizing enzymes in 5-halopyrimidine dehalogenation.
X-ray crystallographic identification of bisulfite-uracil adduct as sodium 5,6-Dihydrouracil 6-sulfonate
Nucleic Acids Symp Ser (Oxf) 2008;(52):451-2.PMID:18776448DOI:10.1093/nass/nrn229.
DNA methylation at position 5 of cytosine residues plays an important role in the gene function control. The analytical method for determining the sites of 5- methylcytosine residues utilizes bisulfite treatment of genomes. Cytosines in DNA are converted into uracils by this treatment, while 5-methylcytosines remain unaltered. The bisulfite treatment followed by amplification by polymerase chain reaction and by sequencing the resulting DNA allows determination of the 5-methylcytosine sites in the original. In this chemical modification, key intermediates are those formed by addition of bisulfite across the 5,6-double bond of pyrimidine ring. Their structures were proposed in 1970 as 5,6-dihydropyrimidine 6-sulfonates, but not its 6-sulfurous acid ester, on the basis of spectral data. X-ray analysis has now been performed for a single crystal of sodium bisulfite-uracil adduct and the results showed its structure as sodium 5,6-Dihydrouracil 6-sulfonate monohydrate, thus providing definite evidence for the C(6)-sulfonate structure.