DOXIFLURIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H11FN2O5
Molecular Weight	246.1924
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=ZWAOHEXOSAUJHY-ZIYNGMLESA-N

InChI=1S/C9H11FN2O5/c1-3-5(13)6(14)8(17-3)12-2-4(10)7(15)11-9(12)16/h2-3,5-6,8,13-14H,1H3,(H,11,15,16)/t3-,5-,6-,8-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/6230419

Doxifluridine is a 5-fluorouracil prodrug that is being tested for the treatment of cancer. The cleavage into 5-fluorouracil occurs enzymatically via a nucleoside phosphorylase. Thus, doxifluridine is not active by itself and its antitumor activity is related to its metabolic conversion into 5-fluorouracil. Doxifluridine has neurotoxic adverse effects.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate kinase 2 Target ID: P23919 Gene ID: 1841.0 Gene Symbol: DTYMK Target Organism: Homo sapiens (Human) Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90e0da7-f702-4f09-9488-74f2bb20e9ac	Inhibitor 8297
DNA synthesis involved in DNA replication 7 Target ID: GO:0090592 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90e0da7-f702-4f09-9488-74f2bb20e9ac	Interacts 323
mRNA transcription 1 Target ID: GO:0009299 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90e0da7-f702-4f09-9488-74f2bb20e9ac	Interacts 323

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastric cancer 53 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23449357	Primary		Withdrawn	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Doxifluridine (5'-dFUrd) in patients with advanced colorectal carcinoma. A phase II study.	1985	2990750
Neurological manifestations in a phase 2 study of 13 patients treated with doxyfluridine.	1985 Aug	2996281
Phase II clinical evaluation of doxifluridine.	1986 Jun	2942245
Transfection of thymidine phosphorylase cDNA to human hepatocellular carcinoma cells enhances sensitivity to fluoropyrimidine but augments endothelial cell migration.	2005 Aug	15864645
Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs.	2006 Jun	16734730
Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency.	2006 Mar	16646564

Patents

Sample Use Guides

In Vivo Use Guide

460-600mg/m2/day per oral (Gastric cancer)

Route of Administration: Oral

In Vitro Use Guide

The cytotoxicity of Doxifluridine was determined in several cultured human tumor lines including tumors of the breast (47-DN, MCF-7), the colon (HCT-8), and the pancreas (Coto-357), as well as an osteosarcoma (MG-63) and a leukemia (HL-60). In vitro clonogenic assays were used to measure cytotoxicity following a 3hr drug exposure. Doxifluridine was less potent than was 5-fluorouracil or 5-fluoro-2'-deoxyuridine in all cells examined, exhibiting its best activity against the 47-DN [concentration that prevented 50% clonal growth compared to untreated control (LD50) = 32 uM] and MCF-7 (LD50= 35 uM) breast carcinomas and MG63 osteosarcoma (LD50 = 41 uM). Intermediate activity was observed against HCT-8 (LD50 = 200 uM)and Colo-357 (LD50 = 150 uM) gastrointestinal tumors. Doxifluridine had very poor activity against the HL-60 leukemia (LD50 = 470 uM).

Name

Type

Language

DOXIFLURIDINE

Official Name

English

5'-DEOXY-5-FLUOROURIDINE

Systematic Name

English

URIDINE, 5'-DEOXY-5-FLUORO-

Systematic Name

English

NSC-758890

Code

English

5-FLUORO-5'-DEOXYURIDINE

Systematic Name

English

DOXIFLURIDINE [MART.]

Common Name

English

RO 219738

Code

English

Doxifluridine [WHO-DD]

Common Name

English

CAPECITABINE RELATED COMPOUND B [USP-RS]

Common Name

English

1-(.BETA.-D-5-DESOXYRIBOFURANOXYL)-5-FLUORURACIL

Common Name

English

FURTULON

Brand Name

English

FULTURON

Common Name

English

doxifluridine [INN]

Common Name

English

CAPECITABINE RELATED COMPOUND B [USP IMPURITY]

Common Name

English

DOXIFLURIDINE [JAN]

Common Name

English

DOXIFLURIDINE [MI]

Common Name

English

FLUTRON

Common Name

English

RO-219738

Code

English

CAPECITABINE RELATED COMPOUND B

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557