CAS 3094-09-5|Doxifluridine

Introduction：Basic information about CAS 3094-09-5|Doxifluridine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Doxifluridine BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles33
8. Synonyms

Common Name	Doxifluridine
CAS Number	3094-09-5	Molecular Weight	246.192
Density	1.6±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₉H₁₁FN₂O₅	Melting Point	188-192 °C(lit.)
MSDS	ChineseUSA	Flash Point	/

Names

Name	doxifluridine
Synonym	More Synonyms

Doxifluridine BiologicalActivity

Description	Doxifluridine(Ro 21-9738; 5'-DFUR) is a thymidine phosphorylase activator for PC9-DPE2 cells with IC50 of 0.62 μM. IC50 value: 0.62 μM(PC9-DPE2 cell).Target: Nucleoside antimetabolite/analogDoxifluridine is a fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.in vitro: 5'-DFUR's metabolic product(N3-Me-5'-dFUR) was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC-UV) analysis of the incubation mixture[1].in vivo: Administration of 200 mg of Furtulon to 23 beagle dogs, the plasma concentrations of doxifluridine, 5-FU, and 5-FUrd were measured simultaneously, using LC-MS/MS. The parent-metabolite compartment model with first-order absorption and Michaelis-Menten kinetics described the pharmacokinetics of doxifluridine, 5-FU, and 5-FUrd. Michaelis-Menten kinetics sufficiently explained the generation and elimination processes of 5-FU and 5-FUrd[2].Clinical trial: A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer was reported in 2009[3].
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>Nucleoside Antimetabolite/AnalogResearch Areas >>Cancer
References	[1]. Dipartimento di Chimica, Università degli Studi della Basilicata, Potenza, In vitro toxicity of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of doxifluridine: a bioanalytical investigation. J Pharm Biomed Anal. 1998 May;17(1):11-6. [2]. Baek IH, Lee BY, Kim MS, Pharmacokinetic analysis of doxifluridine and its metabolites, 5-fluorouracil and 5-fluorouridine, after oral administration in beagle dogs. Eur J Drug Metab Pharmacokinet. 2013 Apr 7. [3]. Yoshikawa T, Tsuburaya A, Shimada K, A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2009;12(4):212-8.

Description

Doxifluridine(Ro 21-9738; 5'-DFUR) is a thymidine phosphorylase activator for PC9-DPE2 cells with IC50 of 0.62 μM. IC50 value: 0.62 μM(PC9-DPE2 cell).Target: Nucleoside antimetabolite/analogDoxifluridine is a fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.in vitro: 5'-DFUR's metabolic product(N3-Me-5'-dFUR) was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC-UV) analysis of the incubation mixture[1].in vivo: Administration of 200 mg of Furtulon to 23 beagle dogs, the plasma concentrations of doxifluridine, 5-FU, and 5-FUrd were measured simultaneously, using LC-MS/MS. The parent-metabolite compartment model with first-order absorption and Michaelis-Menten kinetics described the pharmacokinetics of doxifluridine, 5-FU, and 5-FUrd. Michaelis-Menten kinetics sufficiently explained the generation and elimination processes of 5-FU and 5-FUrd[2].Clinical trial: A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer was reported in 2009[3].

Related Catalog

Signaling Pathways >>Cell Cycle/DNA Damage >>Nucleoside Antimetabolite/AnalogResearch Areas >>Cancer

References

[1]. Dipartimento di Chimica, Università degli Studi della Basilicata, Potenza, In vitro toxicity of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of doxifluridine: a bioanalytical investigation. J Pharm Biomed Anal. 1998 May;17(1):11-6.

[2]. Baek IH, Lee BY, Kim MS, Pharmacokinetic analysis of doxifluridine and its metabolites, 5-fluorouracil and 5-fluorouridine, after oral administration in beagle dogs. Eur J Drug Metab Pharmacokinet. 2013 Apr 7.

[3]. Yoshikawa T, Tsuburaya A, Shimada K, A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2009;12(4):212-8.

Chemical & Physical Properties

Density	1.6±0.1 g/cm3
Melting Point	188-192 °C(lit.)
Molecular Formula	C₉H₁₁FN₂O₅
Molecular Weight	246.192
Exact Mass	246.065201
PSA	104.55000
LogP	-0.96
Index of Refraction	1.605
InChIKey	ZWAOHEXOSAUJHY-SAAKZLLZSA-N
SMILES	CC1OC(n2cc(F)c(=O)[nH]c2=O)C(O)C1O
Storage condition	-20°C Freezer

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YU7526000

CHEMICAL NAME :: Uridine, 5'-deoxy-5-fluoro-

CAS REGISTRY NUMBER :: 3094-09-5

LAST UPDATED :: 199612

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C9-H11-F-N2-O5

MOLECULAR WEIGHT :: 246.22

WISWESSER LINE NOTATION :: T6NVMVJ EF A- BT5OTJ CQ DQ E1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3390 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 5 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18200 mg/kg/13W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - proteinuria Endocrine - changes in thymus weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 7 gm/kg/5W-I

TOXIC EFFECTS :: Endocrine - changes in thymus weight Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15470 mg/kg/26W-I

TOXIC EFFECTS :: Blood - normocytic anemia Blood - changes in bone marrow (not otherwise specified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2100 mg/kg/7D-I

TOXIC EFFECTS :: Endocrine - changes in thymus weight Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1365 mg/kg/13W-I

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Liver - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 550 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1100 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2200 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5950 mg/kg

SEX/DURATION :: male 14 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Rodent - mouse Leukocyte

DOSE/DURATION :: 615 umol/L

REFERENCE :: CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929- Volume(issue)/page/year: 49,2551,1984

Safety Information

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes	Xi: Irritant;
Risk Phrases	R36/37/38
Safety Phrases	26-36
RIDADR	NONH for all modes of transport
WGK Germany	2
RTECS	YU7526000
HS Code	2934999090

Customs

HS Code	2934999090
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles33

Properties of human central nervous system neurons in a glia-depleted (isolated) culture system.

J. Neurosci. Methods 253 , 142-50, (2015)

Current methods for studying human neurons depend on a feeder layer of astroglia supplemented with animal serum to support the growing neurons. These requirements undermine many of the advantages prov...

Occurrence and fate of selected anticancer, antimicrobial, and psychotropic pharmaceuticals in an urban river in a subcatchment of the Yodo River basin, Japan.

Environ. Sci. Pollut. Res. Int. 22 , 18676-86, (2015)

Pollution status of six anticancer agents in the river water and effluents of sewage treatment plants (STPs) in Japan was surveyed with comparative analysis of the levels of four microbial and one psy...

An in vitro liver model on microfluidic device for analysis of capecitabine metabolite using mass spectrometer as detector.

Biosens. Bioelectron. 68 , 322-8, (2015)

In this work, an in vitro liver model in a microfluidic device to imitate and detect prodrug metabolism was developed. A widely used prodrug capecitabine (CAP), which needs to be metabolized into acti...

Synonyms

5-Fluorodesoxyuridine

RO-21-9738

EINECS 221-440-1

doxifluridine

5'DFURD

Uridine, 5'-deoxy-5-fluoro-

Flutron

Furtulon

1-(5-Deoxy-β-D-ribofuranosyl)-5-fluorouracil

5'-DFUR

doxyfluridine

1-(b-D-5'-Deoxyribofuranosyl)-5-fluorouracil

5-Fluoro-5'-deoxyuridine

5'-Deoxy-5-fluorouridine

MFCD00866530

5'-dFUrd

5'-DEOXYFLUOROURIDINE

(+)-5-Fluoro-5'-deoxyuridine

Doxifluidine

DOXIFLUIRDINE

Recommended......