URIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H12N2O6
Molecular Weight	244.2017
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cn([C@@]2([H])[C@@]([H])([C@@]([H])([C@@]([H])(CO)O2)O)O)c(=O)nc1O

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdfhttps://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/27354750
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cell death 7 Target ID: GO:0008219 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf	Inhibitor 7728
Uridine-cytidine kinase 3 Target ID: CHEMBL3542438 Sources: https://www.ncbi.nlm.nih.gov/pubmed/5782006 \| http://www.genome.jp/dbget-bin/www_bget?enzyme+2.7.1.48	Substrate 609
Uridine phosphorylase 1 2 Target ID: CHEMBL4811 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7488099 \| http://www.genome.jp/dbget-bin/www_bget?enzyme+2.4.2.3	Substrate 609
uridine phosphorylase 2 2 Target ID: 151531.0 Gene Symbol: UPP2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7488099 \| http://www.genome.jp/dbget-bin/www_bget?enzyme+2.4.2.3	Substrate 609
RNA 17 Target ID: CHEMBL2311222 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf	Interacts 318

Conditions

Condition	Modality	Highest Phase	Product
Toxicity Due to Chemotherapy (fluorouracil) 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27354750 https://adisinsight.springer.com/drugs/800005276	Curative	Approved 8043	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
Toxicity Due to Chemotherapy (capecitabine) 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27354750 https://adisinsight.springer.com/drugs/800005276	Curative	Approved 8043	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
Orotic aciduria, hereditary 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27354750 https://adisinsight.springer.com/drugs/800005276	Primary	Approved 8043	XURIDEN Approved Use XURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Launch Date 1.44123835E12
Hereditary orotic aciduria 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdf	Primary	Approved 8043	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
Overdose of capecitabine or fluorouracil 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf	Secondary	Approved 8043	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

C_max

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

T_1/2

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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1604 inducer 355	inhibitor 1702 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2A6 627 CYP2B6 717 CYP2C8 818 CYP2C19 1325 CYP2E1 790 CYP3A 191 P-gp 1330	CYP 236	CYP1A2 637 CYP2A6 77 CYP2B6 501 CYP2C8 159 CYP2C19 269 CYP2E1 117 CYP3A 118

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1532	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2A6 659	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 884	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 884	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C19 1392	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C8 865	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 1648	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 1738	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2E1 871	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2E1 871	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A 271	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A 271	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	unlikely

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 236	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208159Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:16704	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16704
ChemicalBook	CB0330400	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0330400
MolPort	MolPort-001-792-520	https://www.molport.com/shop/molecule-link/MolPort-001-792-520
Selleck Chemicals	uridine	http://www.selleckchem.com/products/uridine.html
ZINC	ZINC000002583633	http://zinc15.docking.org/substances/ZINC000002583633
eMolecules	533118	https://www.emolecules.com/cgi-bin/more?vid=533118

PubMed

Title	Date	PubMed
Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons.	2001	11440809
Effects of ATP on intracellular calcium dynamics of neurons and satellite cells in rat superior cervical ganglia.	2001 Apr	11405056
Synthesis of novel 3'-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides.	2001 Apr 20	11304203
Thiosugars. Part 9: synthesis and biological evaluation of some 4'-thio-L-arabino nucleoside analogues.	2001 Apr 23	11327586
High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes.	2001 Apr 5	11334344
Methyl orange antagonizes uridine 5' triphosphate and not alpha,beta-methylene-adenosine 5' triphosphate-evoked depolarization of rat superior cervical ganglia.	2001 Feb	11422572
Natural and synthetic inhibitors of UDP-glucuronosyltransferase.	2001 Feb	11316519
Identification of candidate mitochondrial RNA editing ligases from Trypanosoma brucei.	2001 Feb	11233974
Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression.	2001 Feb	11233740
The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus.	2001 Feb	11161278
Uridine uptake inhibition as a cytotoxicity test for a human hepatoma cell line (HepG2 cells): comparison with the neutral red assay.	2001 Feb 14	11275355
Reduced cellular transport and activation of fluoropyrimidine nucleosides and resistance in human lymphocytic cell lines selected for arabinosylcytosine resistance.	2001 Jan 1	11137707
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	11139404
Synthesis of 2'-modified oligodeoxynucleotides via on-column conjugation.	2001 Jan 26	11429801
Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib).	2001 Jan 26	11032837
Functional production of mammalian concentrative nucleoside transporters in Saccharomyces cerevisiae.	2001 Jan-Mar	11396614
5-(Trifluoromethyl)-beta-l-2'-deoxyuridine, the L-enantiomer of trifluorothymidine: stereospecific synthesis and antiherpetic evaluations.	2001 Jul	11425574
Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide.	2001 Jul	11404290
Apical P2Y4 purinergic receptor controls K+ secretion by vestibular dark cell epithelium.	2001 Jul	11401851
Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses.	2001 Jul 1	11431359
Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins.	2001 Jul 10	11434784
Structure of an RNA hairpin from HRV-14.	2001 Jul 10	11434774
Intracellular trafficking determinants in APOBEC-1, the catalytic subunit for cytidine to uridine editing of apolipoprotein B mRNA.	2001 Jul 15	11426934
Activation pathways of 5-fluorouracil in rat organs and in PC12 cells.	2001 Jul 15	11389880
Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1.	2001 Jul 27	11375981
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	11389924
Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase.	2001 Jul 9	11425530
Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency.	2001 Jun	11426759
Possible existence of a novel receptor for uridine analogues in the central nervous system using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridines.	2001 Jun	11411572
Poly(A) polymerase activity and RNA polyadenylation in Streptomyces coelicolor A3(2).	2001 Jun	11401719
Elucidation of the initial step of oligonucleotide fragmentation in matrix-assisted laser desorption/ionization using modified nucleic acids.	2001 Jun	11401165
Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model.	2001 Jun 1	11380239
Structure of a C-rich strand fragment of the human centromeric satellite III: a pH-dependent intercalation topology.	2001 Jun 1	11371167
Fluoropyrimidine sensitivity of human MCF-7 breast cancer cells stably transfected with human uridine phosphorylase.	2001 Jun 15	11401323
Active intestinal absorption of nucleosides by Na+-dependent transport across the brush border membrane in cows.	2001 Mar	11286414
Uridine insertion/deletion RNA editing in Leishmania tarentolae mitochondria shows cell cycle dependence.	2001 Mar	11254966
Successful living-donor liver transplantation from an asymptomatic carrier mother in ornithine transcarbamylase deficiency.	2001 Mar	11241058
Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis.	2001 Mar	11231942
Nucleotides U28-A42 and A37 in unmodified yeast tRNA(Trp) as negative identity elements for bovine tryptophanyl-tRNA synthetase.	2001 Mar 16	11257501
A cis-dominant cyclic nucleotide-dependent regulatory domain in the 3'-untranslated region of Na(+)/glucose cotransporter (SGLT1) mRNA.	2001 Mar 16	11257500
Cytosolic high K(m) 5'-nucleotidase and 5'(3')-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism.	2001 Mar 2	11083867
An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors.	2001 Mar 30	11273702
Indomethacin prevents the induction of inducible nitric oxide synthase in murine peritoneal macrophages and decreases their nitric oxide production.	2001 Mar 9	11292070
Dynamic changes in glucose metabolism accompanying the expression of the neural phenotype after differentiation in PC12 cells.	2001 Mar 9	11245818
The UDPase activity of the Kluyveromyces lactis Golgi GDPase has a role in uridine nucleotide sugar transport into Golgi vesicles.	2001 May	11425802
Detection of genome impairment in bovine early embryos by autoradiography: a methodological note.	2001 May	11358319
Effects of purine and pyrimidine nucleotides on intracellular Ca2+ in human eosinophils: activation of purinergic P2Y receptors.	2001 May	11344352
Lethality of glnD null mutations in Azotobacter vinelandii is suppressible by prevention of glutamine synthetase adenylylation.	2001 May	11320130
Liquid-core waveguide technology for coupling column liquid chromatography and Raman spectroscopy.	2001 May 18	11403453
Probing Tat peptide-TAR RNA interactions by psoralen photo-cross-linking.	2001 May 29	11371209

Patents

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.

Name

Type

Language

URIDINE

Official Name

English

URACIL RIBOSIDE

Common Name

English

URIDINE [INCI]

Common Name

English

URIDINE [WHO-DD]

Common Name

English

URIDINE [MI]

Common Name

English

ADENOSINE IMPURITY F [EP]

Common Name

English

1-.BETA.-D-RIBOFURANOSYLURACIL

Common Name

English

NSC-20256

Code

English

URIDINE [USP-RS]

Common Name

English

URIDINE [MART.]

Common Name

English

Classification Tree Code System Code

LOINC

59216-2