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Doxifluridine

Names

[ CAS No. ]:
3094-09-5

[ Name ]:
Doxifluridine

[Synonym ]:
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

Biological Activity

[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/Analog
Research 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.


[Related Small Molecules]

Azacitidine (5-Azacytidine) | Broxuridine | Forodesine (hydrochloride) | Floxuridine | Raltitrexed | Trifluorothymidine | Vidarabine | Tipiracil hydrochloride | Clofarabine | Nelarabine | 8-Azaguanine | RX-3117 | Tegafur | LY2334737 | Carmofur

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

[ Storage condition ]:
-20°C Freezer

MSDS

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%

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