Uridine triacetate
(Synonyms: 2',3',5'-三乙酰尿苷,Tri-O-acetyl uridine) 目录号 : GC38302
A prodrug of uridine
Cas No.:4105-38-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
2’,3’,5’-Triacetyluridine is a prodrug of uridine .1 It is more lipid soluble than uridine and resistant to degradation by uridine phosphorylase. It is cleaved by plasma esterases in vivo to release uridine. 2’,3’,5’-Triacetyluridine (6% in the diet) decreases neurodegeneration in the piriform cortex and striatum, as well as reduces the amount of huntingtin-positive aggregates and increases BDNF protein levels in the piriform cortex in a transgenic mouse model of Huntington’s disease.2 It also improves rotarod performance and increases survival in transgenic mouse models of Huntington’s disease. 2’,3’,5’-Triacetyluridine reverses toxicity and increases survival in a mouse model of dihydropyrimidine dehydrogenase (DPD) deficiency-induced 5-fluorouracil overdose when used at a concentration of 2,000 mg/kg three times per day beginning within 24 hours of 5-FU administration.3 Formulations containing 2’,3’,5’-triacetyluridine have been used in the treatment of hereditary orotic aciduria and of overdose or life-threatening toxicity due to flurouracil or capecitabine.
1.Ashour, O.M., Naguib, F.N.M., and el Kouni, M.H.5-(m-Benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2',3',5'-tri-O-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration: Implications for chemotherapyBiochem. Pharmacol.51(12)1601-1611(1996) 2.Saydoff, J.A., Garcia, R.A.G., Browne, S.E., et al.Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's diseaseNeurobiol. Dis.24(3)455-465(2006) 3.von Borstel, R.W., O'Neil, J.D., Saydoff, J.A., et al.Uridine triacetate for lethal 5-FU toxicity due to dihydropyrimidine dehydrogenase (DPD) deficiencyJ. Clin. Oncol.28(15_supp)e13505-e13505(2010)
| Cas No. | 4105-38-8 | SDF | |
| 别名 | 2',3',5'-三乙酰尿苷,Tri-O-acetyl uridine | ||
| Canonical SMILES | O=C(NC(C=C1)=O)N1[C@H](O2)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@H]2COC(C)=O | ||
| 分子式 | C15H18N2O9 | 分子量 | 370.31 |
| 溶解度 | DMSO: ≥ 100 mg/mL (270.04 mM); Water: 10 mg/mL (27.00 mM) | 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 | 2.7004 mL | 13.5022 mL | 27.0044 mL |
| 5 mM | 0.5401 mL | 2.7004 mL | 5.4009 mL |
| 10 mM | 0.27 mL | 1.3502 mL | 2.7004 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。
Uridine triacetate
Hosp Pharm 2016 Jun;51(6):484-8.PMID:27354750DOI:10.1310/hpj5106-484.
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The June 2016 monograph topics are elbasvir/grazoprevir, ixekizumab, brivaracetam, reslizumab, and sofosbuvir/velpatasvir. The Safety MUE is on reslizumab.
FDA Approval: Uridine triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs
Clin Cancer Res 2016 Sep 15;22(18):4545-9.PMID:27401247DOI:10.1158/1078-0432.CCR-16-0638.
On December 11, 2015, the FDA approved Uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of Uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving Uridine triacetate (10 g or 6.2 g/m(2) orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life-threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of Uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-49. ©2016 AACR.
Successful use of Uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature
J Oncol Pharm Pract 2019 Jan;25(1):234-238.PMID:28950804DOI:10.1177/1078155217732141.
5-fluorouracil and capecitabine are chemotherapeutic agents commonly used to treat solid malignancies. Increased susceptibility to 5-fluorouracil or capecitabine, caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, or other genetic mutations in the enzymes that metabolize 5-fluorouracil can lead to severe life-threatening toxicities and are typically manifested by an early onset of symptoms. We report and discuss the management and outcome of capecitabine toxicity with the recently FDA approved antidote, Uridine triacetate (Vistogard), in a 57-year-old female breast cancer patient with homozygous dihydropyrimidine dehydrogenase deficiency who received treatment beyond the recommended 96 h window from the last dose of capecitabine.
Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?
J Oncol Pharm Pract 2020 Apr;26(3):747-753.PMID:31382864DOI:10.1177/1078155219865597.
Fluoropyrimidine-based regimens are among the most commonly used chemotherapy combinations for the treatment of solid tumors. Several genetic polymorphisms that are implicated with fluoropyrimidine anabolism and catabolism have been associated with the development of life-threatening toxicities. Uridine triacetate is an FDA-approved antidote for 5-fluorouracil or capecitabine overdose and early-onset, life-threatening toxicity within 96 h of last chemotherapy dose. To date, it is not accessible for Greek patients as per the current summary of product characteristic's time restrictions. We report and discuss the course and outcome of capecitabine toxicity in a 66-year-old female colorectal cancer patient with heterozygous dihydropyrimidine dehydrogenase deficiency. This paper highlights the difficulty in timely access of this lifesaving medication for Greek and possibly other European patients.
Fluoropyrimidine-induced cardiotoxicity
Crit Rev Oncol Hematol 2018 Apr;124:1-10.PMID:29548480DOI:10.1016/j.critrevonc.2018.02.002.
Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs, widely used for the treatment of a variety of cancers, both in adjuvant and in metastatic setting. Although the most common toxicities of these drugs have been extensively studied, robust data and comprehensive characterization still lack concerning fluoropyrimidine-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity. This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, Uridine triacetate. The role of alternative chemotherapeutic options, namely raltitrexed and TAS-102, is discussed, and, lastly, we overview the most promising future directions in the research on FIC and development of diagnostic tools, including microRNA technology.