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

Molecular Formula	C9H11FN2O5
Molecular Weight	246.1924
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

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Gastric cancer 53 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23449357	Primary		Withdrawn	Unknown Approved Use Unknown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
[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].	2000 Aug	10969600
Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.	2003 Sep 15	12941330
[Enhancement effect of interferon gamma on the sensitivity of RT4 bladder cancer cells to 5'-deoxy-5-fluorouridine,and 5-fluorouracil through up-regulation of PD-ECGF/TP].	2004 Aug	15301717
Modulation of uridine phosphorylase gene expression by tumor necrosis factor-alpha enhances the antiproliferative activity of the capecitabine intermediate 5'-deoxy-5-fluorouridine in breast cancer cells.	2006 Apr	16397116
Induction of thymidine phosphorylase expression by AZT contributes to enhancement of 5'-DFUR cytotoxicity.	2006 Dec 8	16457948
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
[Interferon alpha enhances the sensitivity of SMMC-7721 hepatocellular carcinoma cells to 5'-deoxy-5-fluorouridine related to up-regulation of thymidine phosphorylase].	2007 Aug 14	17988526
Changes of gene expression of thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase after the administration of 5'-deoxy-5-fluorouridine, paclitaxel and its combination in human gastric cancer xenografts.	2008 May-Jun	18630517
Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans--toxicological implications.	2011 Aug	21804305
Src: a potential target for the treatment of triple-negative breast cancer.	2011 Oct	21357651

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).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:53:07 UTC 2023` Edited by `admin` on `Fri Dec 15 15:53:07 UTC 2023`
Record UNII	V1JK16Y2JP
Record Status	`Validated (UNII)`
Record Version

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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