Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C15H18N2O9 |
| Molecular Weight | 370.3114 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)OC[C@H]1O[C@H]([C@H](OC(C)=O)[C@@H]1OC(C)=O)N2C=CC(=O)NC2=O
InChI
InChIKey=AUFUWRKPQLGTGF-FMKGYKFTSA-N
InChI=1S/C15H18N2O9/c1-7(18)23-6-10-12(24-8(2)19)13(25-9(3)20)14(26-10)17-5-4-11(21)16-15(17)22/h4-5,10,12-14H,6H2,1-3H3,(H,16,21,22)/t10-,12-,13-,14-/m1/s1
| Molecular Formula | C15H18N2O9 |
| Molecular Weight | 370.3114 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27354750http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdfCurator's Comment: description was created based on several sources, including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
http://www.rxlist.com/xuriden-drug.htm
https://www.drugs.com/mtm/uridine-triacetate.html
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27354750http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdf
Curator's Comment: description was created based on several sources, including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
http://www.rxlist.com/xuriden-drug.htm
https://www.drugs.com/mtm/uridine-triacetate.html
Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.
CNS Activity
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18540779https://www.ncbi.nlm.nih.gov/pubmed/16769123
Curator's Comment: Uridine triacetate is CNS penetrant and active.
Uridine triacetate is an acetylated prodrug of uridine. Circulating uridine is taken up into mammalian cells via specific nucleoside transporters, and also crosses the blood-brain barrier.
Uridine triacetate treatment may decrease symptoms of depression.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: GO:0008219 |
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Target ID: CHEMBL3542438 |
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Target ID: 151531.0 Gene Symbol: UPP2 |
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Target ID: CHEMBL2311222 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | VISTOGARD Approved UseVISTOGARD® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients:
• following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
• who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or earlyonset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration Launch Date2015 |
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| Curative | VISTOGARD Approved UseVISTOGARD® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients:
• following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
• who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or earlyonset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration Launch Date2015 |
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| Primary | XURIDEN Approved UseXURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Launch Date2015 |
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| Primary | XURIDEN Approved UseXURIDEN™ is indicated for the treatment of hereditary orotic aciduria. XURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. (1) Launch Date2015 |
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| Secondary | VISTOGARD Approved UseVISTOGARD® is indicated for the emergency treatment of adult and pediatric patients:
following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
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. Launch Date2015 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
36.1 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
25.8 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
164.1 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
79 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.38 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. | 2000 Jan-Feb |
|
| Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons. | 2001 |
|
| Analysis of RNA synthesis by cytometry. | 2001 |
|
| Effects of ATP on intracellular calcium dynamics of neurons and satellite cells in rat superior cervical ganglia. | 2001 Apr |
|
| Synthesis of novel 3'-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides. | 2001 Apr 20 |
|
| Thiosugars. Part 9: synthesis and biological evaluation of some 4'-thio-L-arabino nucleoside analogues. | 2001 Apr 23 |
|
| Gap-junctional communication between feeder cells and recipient normal epithelial cells correlates with growth stimulation. | 2001 Feb |
|
| Natural and synthetic inhibitors of UDP-glucuronosyltransferase. | 2001 Feb |
|
| Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression. | 2001 Feb |
|
| The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus. | 2001 Feb |
|
| A novel proton-dependent nucleoside transporter, CeCNT3, from Caenorhabditis elegans. | 2001 Feb |
|
| Importance of specific nucleotides in the folding of the natural form of the hairpin ribozyme. | 2001 Feb 20 |
|
| The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils generates 5-bromouracil, a mutagenic thymine analogue. | 2001 Feb 20 |
|
| A base change in the catalytic core of the hairpin ribozyme perturbs function but not domain docking. | 2001 Feb 27 |
|
| Determination of nucleosides in natural Cordyceps sinensis and cultured Cordyceps mycelia by capillary electrophoresis. | 2001 Jan |
|
| Activation pathways of 5-fluorouracil in rat organs and in PC12 cells. | 2001 Jul 15 |
|
| Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1. | 2001 Jul 27 |
|
| Effect of 17-beta estradiol and epidermal growth factor on DNA and RNA labeling in astroglial cells during development, maturation and differentiation in culture. | 2001 Jul 31 |
|
| Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency. | 2001 Jun |
|
| P2Y receptor-mediated inhibition of voltage-activated Ca(2+) currents in PC12 cells. | 2001 Mar |
|
| Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis. | 2001 Mar |
|
| Ontogenic and longitudinal activity of Na(+)-nucleoside transporters in the human intestine. | 2001 Mar |
|
| Nucleotides U28-A42 and A37 in unmodified yeast tRNA(Trp) as negative identity elements for bovine tryptophanyl-tRNA synthetase. | 2001 Mar 16 |
|
| Dynamic changes in glucose metabolism accompanying the expression of the neural phenotype after differentiation in PC12 cells. | 2001 Mar 9 |
|
| Effects of purine and pyrimidine nucleotides on intracellular Ca2+ in human eosinophils: activation of purinergic P2Y receptors. | 2001 May |
|
| Stimulation of cardiac L-type calcium channels by extracellular ATP. | 2001 May |
|
| Bacteriophage T7 RNA polymerase transcription elongation is inhibited by site-specific, stereospecific benzo[c]phenanthrene diol epoxide DNA lesions. | 2001 May 1 |
|
| High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5'-diphosphate-glucuronosyltransferase. | 2001 May 15 |
|
| Probing Tat peptide-TAR RNA interactions by psoralen photo-cross-linking. | 2001 May 29 |
|
| 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. | 2019 Jan |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
Curator's Comment: 10 grams orally every 6 hours for 20 doses, without regard to meals.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
The recommended starting dosage of oral XURIDEN for the treatment of hereditary orotic aciduria is 60 mg/kg once daily. Increase the dosage of
XURIDEN to 120 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy.
The recommended dosage of VISTOGARD for the emergency treatment of fluorouracil or capecitabine overdose.
Adults: 10 grams (1 packet) orally every 6 hours for 20 doses, without regard to meals.
Pediatric: 6.2 grams/m2 of body surface area (not to exceed 10 grams per dose) orally every 6 hours
for 20 doses, without regard to meals.
Route of Administration:
Oral
Uridine dose-dependently protected cells from chemical hypoxia and ceramide, and decreased formation of reactive oxygen species and mitochondrial DNA damage due to hydrogen peroxide. These protective effects were achieved by raising uridine levels to at least 25-50 μM and serum uridine levels in this range in humans were obtained with oral uridine prodrug PN401 (Uridine triacetate).
| Substance Class |
Chemical
Created
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| Record UNII |
2WP61F175M
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| Record Status |
Validated (UNII)
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FDA ORPHAN DRUG |
273808
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WHO-ATC |
A16AX13
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FDA ORPHAN DRUG |
163202
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FDA ORPHAN DRUG |
401013
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DSLD |
4456 (Number of products:3)
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NCI_THESAURUS |
C1557
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EU-Orphan Drug |
EU/3/09/637
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FDA ORPHAN DRUG |
290009
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DB09144
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20058
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DTXSID40961409
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WW-18
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90914
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4105-38-8
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2WP61F175M
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5029
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2WP61F175M
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CHEMBL2107381
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1665222
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100000175259
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C2379
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Uridine triacetate
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223-881-5
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9204
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m11852
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Biological Half-life | PHARMACOKINETIC |
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