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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12N2O6
Molecular Weight 244.2014
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of URIDINE

SMILES

OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=CC(=O)NC2=O

InChI

InChIKey=DRTQHJPVMGBUCF-XVFCMESISA-N
InChI=1S/C9H12N2O6/c12-3-4-6(14)7(15)8(17-4)11-2-1-5(13)10-9(11)16/h1-2,4,6-8,12,14-15H,3H2,(H,10,13,16)/t4-,6-,7-,8-/m1/s1

HIDE SMILES / InChI

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
VISTOGARD
Curative
VISTOGARD
Primary
XURIDEN
Primary
XURIDEN
Secondary
VISTOGARD

Cmax

ValueDoseCo-administeredAnalytePopulation
36.1 μM
4.15 g single, oral
URIDINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
164.1 μM × h
4.15 g single, oral
URIDINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
4.6 h
4.15 g single, oral
URIDINE plasma
Homo sapiens

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.