Trifluorothymidine

Names

[ CAS No. ]:
70-00-8

[ Name ]:
Trifluorothymidine

[Synonym ]:
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxyméthyl)tétrahydrofuran-2-yl]-5-(trifluorométhyl)pyrimidine-2,4(1H,3H)-dione
Viroptic
α,α,α-Trifluorothymidine
2'-Deoxy-5-(trifluoromethyl)uridine
UNII-RMW9V5RW38
Trifluorothymidine
1-(2-Deoxy-β-D-glycero-pentofuranosyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione
Trifluridine
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione
EINECS 200-722-8
1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-(trifluormethyl)pyrimidin-2,4(1H,3H)-dion
2,4(1H,3H)-Pyrimidinedione, 1-(2-deoxy-β-D-ribofuranosyl)-5-(trifluoromethyl)-
2,4(1H,3H)-pyrimidinedione, 1-(2-deoxy-β-D-glycero-pentofuranosyl)-5-(trifluoromethyl)-
2'-Deoxy-5-trifluoromethyluridine
Virophta
Uridine, 2'-deoxy-5-(trifluoromethyl)-
a,a,a-Trifluorothymidine
MFCD00006534

Biological Activity

[Description]:

Trifluridine is an irreversible thymidylate synthase inhibitor, and thereby suppresses DNA synthesis. Trifluridine is an antiviral drug for herpes simplex virus (HSV) infection.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Signaling Pathways >> Apoptosis >> Thymidylate Synthase

Research Areas >> Cancer

[References]

[1]. Suzuki N, et al. Mode of action of trifluorothymidine (TFT) against DNA replication and repair enzymes. Int J Oncol. 2011 Jul;39(1):263-70.

[2]. Suzuki N, et al. Trifluorothymidine exhibits potent antitumor activity via the induction of DNA double-strand breaks. Exp Ther Med. 2011 May;2(3):393-397.

[3]. Temmink OH, et al. Irinotecan-induced cytotoxicity to colon cancer cells in vitro is stimulated by pre-incubation withtrifluorothymidine. Eur J Cancer. 2007 Jan;43(1):175-83.

[4]. Okayama T, et al. Involvement of concentrative nucleoside transporter 1 in intestinal absorption of trifluorothymidine, a novel antitumor nucleoside, in rats. J Pharmacol Exp Ther. 2012 Feb;340(2):457-62.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Melting Point ]:
190-193 °C(lit.)

[ Molecular Formula ]:
C₁₀H₁₁F₃N₂O₅

[ Molecular Weight ]:
296.200

[ Exact Mass ]:
296.062012

[ PSA ]:
104.55000

[ LogP ]:
0.07

[ Index of Refraction ]:
1.534

[ Storage condition ]:
−20°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XP2087500

CHEMICAL NAME :: Thymidine, alpha,alpha,alpha-trifluoro-

CAS REGISTRY NUMBER :: 70-00-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C10-H11-F3-N2-O5

MOLECULAR WEIGHT :: 296.23

WISWESSER LINE NOTATION :: T6NVMVJ EXFFF A- ET5OTJ B1Q CQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2946 mg/kg

TOXIC EFFECTS :: Liver - other changes

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1931 mg/kg

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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3381 mg/kg

TOXIC EFFECTS :: Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 400 mg/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 :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 187 mg/kg/15D-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of salivary glands Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - leukopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 2600 mg/kg/90D-I

TOXIC EFFECTS :: Liver - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 2100 mg/kg/14D-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - chronic pulmonary edema Gastrointestinal - hypermotility, diarrhea Related to Chronic Data - death

MUTATION DATA

TYPE OF TEST :: Mutation in mammalian somatic cells

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 4 mg/L

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 86,180,1986 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3218 No. of Facilities: 3 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 82 (estimated) No. of Female Employees: 14 (estimated)

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302 + H312 + H332-H351

[ Precautionary Statements ]:
P261-P280-P301 + P312 + P330

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi:Irritant

[ Risk Phrases ]:
R20/21/22;R40

[ Safety Phrases ]:
S22-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
XP2087500

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex m...

Quantitative high-throughput identification of drugs as modulators of human constitutive androstane receptor.

Sci. Rep. 5 , 10405, (2015)

The constitutive androstane receptor (CAR, NR1I3) plays a key role in governing the transcription of numerous hepatic genes that involve xenobiotic metabolism/clearance, energy homeostasis, and cell p...

Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells.

Int. J. Cancer 126 , 2457-2468, (2010)

Trifluorothymidine (TFT) is part of the oral drug formulation TAS-102. Both 5-fluorouracil (5-FU) and TFT can inhibit thymidylate synthase and be incorporated into DNA. TFT shows only moderate cross-r...