U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of URIDINE TRIACETATE

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

HIDE SMILES / InChI

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

Description
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 (formally PN401) is an acetylated prodrug of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine triacetate under VISTOGARD trade name is a uridine replacement agent approved for the emergency treatment of fluorouracil or capecitabine overdose (regardless of the presence of symptoms) or early-onset severe or life-threatening cardiac or central nervous system (CNS) toxicity and/or early-onset unusually severe adverse reactions (eg, gastrointestinal [GI] toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration in adult and pediatric patients. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Fluorouracil is a cytotoxic antimetabolite that interferes with nucleic acid metabolism in normal and cancer cells. Cells anabolize fluorouracil to the cytotoxic intermediates 5-fluoro-2’-deoxyuridine-5’- monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits thymidylate synthase, blocking thymidine synthesis. Thymidine is required for DNA replication and repair. Uridine is not found in DNA. The second source of fluorouracil cytotoxicity is the incorporation of its metabolite, FUTP, into RNA. This incorporation of FUTP into RNA is proportional to systemic fluorouracil exposure. Excess circulating uridine derived from VISTOGARD is converted into uridine triphosphate (UTP), which competes with FUTP for incorporation into RNA. Uridine triacetate is also approved for the treatment of hereditary orotic aciduria under XURIDEN trade name. Uridine triacetate provides uridine in the systemic circulation of patients with hereditary orotic aciduria who cannot synthesize adequate quantities of uridine due to a genetic defect in uridine nucleotide synthesis.

CNS Activity

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

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
VISTOGARD

Approved Use

VISTOGARD® 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 Date

1.4497056E12
Curative
VISTOGARD

Approved Use

VISTOGARD® 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 Date

1.4497056E12
Primary
XURIDEN

Approved Use

XURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria.

Launch Date

1.44123835E12
Primary
XURIDEN

Approved Use

XURIDEN™ 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 Date

1.44132486E12
Secondary
VISTOGARD

Approved Use

VISTOGARD® 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 Date

1.4497056E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
36.1 μM
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
164.1 μM × h
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
4.6 h
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
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
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
unlikely
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
PubMed

PubMed

TitleDatePubMed
Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitor-resistant (mENT2) equilibrative nucleoside transporters from mouse brain.
2000 Dec 1
Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons.
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
Natural and synthetic inhibitors of UDP-glucuronosyltransferase.
2001 Feb
Identification of candidate mitochondrial RNA editing ligases from Trypanosoma brucei.
2001 Feb
Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression.
2001 Feb
Purine and pyrimidine nucleotide-sensitive phospholipase A(2) in ampulla from frog semicircular canal.
2001 Feb
Peptide-triggered conformational switch in HIV-1 RRE RNA complexes.
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
The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea-pig uterus.
2001 Feb
Uridine uptake inhibition as a cytotoxicity test for a human hepatoma cell line (HepG2 cells): comparison with the neutral red assay.
2001 Feb 14
Extracellular adenosine-induced apoptosis in mouse neuroblastoma cells: studies on involvement of adenosine receptors and adenosine uptake.
2001 Feb 15
The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils generates 5-bromouracil, a mutagenic thymine analogue.
2001 Feb 20
Synthesis using ring closure metathesis and effect on nucleoside transport of a (N)-methanocarba S-(4-nitrobenzyl)thioinosine derivative.
2001 Feb 22
5-Formyluracil and its nucleoside derivatives confer toxicity and mutagenicity to mammalian cells by interfering with normal RNA and DNA metabolism.
2001 Feb 3
Arrangement of the central pseudoknot region of 16S rRNA in the 30S ribosomal subunit determined by site-directed 4-thiouridine crosslinking.
2001 Jan
Determination of nucleosides in natural Cordyceps sinensis and cultured Cordyceps mycelia by capillary electrophoresis.
2001 Jan
Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes.
2001 Jan
Reduced cellular transport and activation of fluoropyrimidine nucleosides and resistance in human lymphocytic cell lines selected for arabinosylcytosine resistance.
2001 Jan 1
Identification of Cys140 in helix 4 as an exofacial cysteine residue within the substrate-translocation channel of rat equilibrative nitrobenzylthioinosine (NBMPR)-insensitive nucleoside transporter rENT2.
2001 Jan 15
Amino acid residues in ribonuclease MC1 from bitter gourd seeds which are essential for uridine specificity.
2001 Jan 16
Functional production of mammalian concentrative nucleoside transporters in Saccharomyces cerevisiae.
2001 Jan-Mar
Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses.
2001 Jul 1
Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins.
2001 Jul 10
Structure of an RNA hairpin from HRV-14.
2001 Jul 10
Intracellular trafficking determinants in APOBEC-1, the catalytic subunit for cytidine to uridine editing of apolipoprotein B mRNA.
2001 Jul 15
Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1.
2001 Jul 27
Elucidation of the initial step of oligonucleotide fragmentation in matrix-assisted laser desorption/ionization using modified nucleic acids.
2001 Jun
Differential effects of apical and basolateral uridine triphosphate on intestinal epithelial chloride secretion.
2001 Jun
Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model.
2001 Jun 1
Fluoropyrimidine sensitivity of human MCF-7 breast cancer cells stably transfected with human uridine phosphorylase.
2001 Jun 15
Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria.
2001 Jun 29
The effect of cytidine on the structure and function of an RNA ligase ribozyme.
2001 Mar
Uridine insertion/deletion RNA editing in Leishmania tarentolae mitochondria shows cell cycle dependence.
2001 Mar
Successful living-donor liver transplantation from an asymptomatic carrier mother in ornithine transcarbamylase deficiency.
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
Synthesis and separation of diastereomers of uridine 2',3'-cyclic boranophosphate.
2001 Mar 12
An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors.
2001 Mar 30
Indomethacin prevents the induction of inducible nitric oxide synthase in murine peritoneal macrophages and decreases their nitric oxide production.
2001 Mar 9
Identification and quantification of base and nucleoside markers in extracts of Ganoderma lucidum, Ganoderma japonicum and Ganoderma capsules by micellar electrokinetic chromatography.
2001 Mar 9
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
Lethality of glnD null mutations in Azotobacter vinelandii is suppressible by prevention of glutamine synthetase adenylylation.
2001 May
Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases.
2001 May
Uridine receptor: discovery and its involvement in sleep mechanism.
2001 May 1
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
Patents

Sample Use Guides

In Vivo Use Guide
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 starting dosage is 60 mg/kg once daily; the dose may be increased to120 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy.
Route of Administration: Oral
At very high levels (10–200 ìM) in vitro uridine decreases azide and H2O2 toxicity in fibroblasts from patients with Alzheimer disease and in human neuroprogenitor cells.
Substance Class Chemical
Created
by admin
on Thu Jul 06 21:58:22 UTC 2023
Edited
by admin
on Thu Jul 06 21:58:22 UTC 2023
Record UNII
2WP61F175M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
URIDINE TRIACETATE
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
VISTOGARD
Brand Name English
RG2133
Code English
XURIDEN
Brand Name English
Uridine triacetate [WHO-DD]
Common Name English
TRIACETYL URIDINE
Systematic Name English
uridine triacetate [INN]
Common Name English
TRIACETYLURIDINE
Systematic Name English
RG-2133
Code English
URIDINE TRIACETATE [MI]
Common Name English
VISTONURIDINE
Common Name English
PN401
Code English
URIDINE TRIACETATE [USAN]
Common Name English
2',3',5'-TRI-O-ACETYLURIDINE
Systematic Name English
URIDINE TRIACETATE [ORANGE BOOK]
Common Name English
PN-401
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 273808
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
WHO-ATC A16AX13
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
FDA ORPHAN DRUG 163202
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
FDA ORPHAN DRUG 401013
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
DSLD 4456 (Number of products:3)
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
NCI_THESAURUS C1557
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
EU-Orphan Drug EU/3/09/637
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
FDA ORPHAN DRUG 290009
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
Code System Code Type Description
DRUG BANK
DB09144
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
PUBCHEM
20058
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID40961409
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
USAN
WW-18
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
CHEBI
90914
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
CAS
4105-38-8
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
FDA UNII
2WP61F175M
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
DRUG CENTRAL
5029
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
DAILYMED
2WP61F175M
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL2107381
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
RXCUI
1665222
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY RxNorm
SMS_ID
100000175259
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
NCI_THESAURUS
C2379
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
WIKIPEDIA
Uridine triacetate
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
ECHA (EC/EINECS)
223-881-5
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
INN
9204
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
MERCK INDEX
M11852
Created by admin on Thu Jul 06 21:58:22 UTC 2023 , Edited by admin on Thu Jul 06 21:58:22 UTC 2023
PRIMARY
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC