Identification

Name
Trifluridine
Accession Number
DB00432  (APRD01275)
Type
Small Molecule
Groups
Approved
Description

An antiviral derivative of thymidine used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557)

Structure
Thumb
Synonyms
  • 5-(Trifluoromethyl)deoxyuridine
  • 5-Trifluoromethyl-2-deoxyuridine
  • F₃T
  • TFT
  • Trifluoromethyldeoxyuridine
  • Trifluorothymidine
  • Trifluorothymine deoxyriboside
  • Trifluridin
  • Trifluridina
  • Trifluridine
  • Trifluridinum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sandoz TrifluridineSolution1 %OphthalmicSandoz Canada Incorporated2004-01-23Not applicableCanada
TrifluridineSolution1 g/100mLOphthalmicGreenstone, Llc1980-04-102017-11-30Us
ViropticSolution1 %OphthalmicValeant Canada Lp Valeant Canada S.E.C.1987-12-31Not applicableCanada
ViropticSolution1 g/100mLOphthalmicPfizer Laboratories Div Pfizer Inc.1980-04-10Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-trifluridine Ophthalmic SolutionSolution1 %OphthalmicApotex CorporationNot applicableNot applicableCanada
TrifluridineSolution10 mg/mLOphthalmicFalcon Pharmaceuticals2001-05-14Not applicableUs
TrifluridineSolution / drops10 mg/mLOphthalmicHi Tech Pharmacal Co., Inc.2017-07-28Not applicableUs
International/Other Brands
Thilol (Pharmex) / Triflumann (Dr. Gerhard Mann) / Triherpine (Medivis) / Virophta (Horus) / Viroptic
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
LonsurfTrifluridine (20 mg/1) + Tipiracil hydrochloride (8.19 mg/1)Tablet, film coatedOralTaisho Pharmaceutical Co., Ltd.2015-09-22Not applicableUs
LonsurfTrifluridine (15 mg/1) + Tipiracil hydrochloride (6.14 mg/1)Tablet, film coatedOralTaisho Pharmaceutical Co., Ltd.2015-09-22Not applicableUs
Categories
UNII
RMW9V5RW38
CAS number
70-00-8
Weight
Average: 296.1999
Monoisotopic: 296.062006087
Chemical Formula
C10H11F3N2O5
InChI Key
VSQQQLOSPVPRAZ-RRKCRQDMSA-N
InChI
InChI=1S/C10H11F3N2O5/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7/h2,5-7,16-17H,1,3H2,(H,14,18,19)/t5-,6+,7+/m0/s1
IUPAC Name
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
OC[[email protected]]1O[[email protected]](C[[email protected]@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F

Pharmacology

Indication

Ophthalmic solution for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.

Structured Indications
Pharmacodynamics

Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. Some strains of adenovirus are also inhibited in vitro. Trifluridine is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, trifluridine was also effective. Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known.

Mechanism of action

The mechanism of action of trifluridine has not been fully determined, but appears to involve the inhibition of viral replication. Trifluridine does this by incorporating into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate. This drug also reversibly inhibits thymidylate synthetase, an enzyme that is necessary for DNA synthesis.

TargetActionsOrganism
AThymidylate synthase
inhibitor
Human
ADNA
other/unknown
Human
Absorption

Systemic absorption of trifluridine following therapeutic dosing with trifluridine ophthalmic appears to be negligible.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

One major metabolite, 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea, indicating localized metabolism.

Route of elimination
Not Available
Half life

Approximately 12 to 18 minutes following ophthalmic administration.

Clearance
Not Available
Toxicity

Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac. Acute overdosage by accidental oral ingestion has not occurred. However, should such ingestion occur, the 75 mg dosage of trifluridine in a 7.5 mL bottle of trifluridine is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD50 in the mouse and rat was 4379 mg/kg or higher.

Affected organisms
  • Human Herpes Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
  1. Costin D, Dogaru M, Popa AS, Cijevschi I: [Trifluridine therapy in herpetic in keratitis]. Rev Med Chir Soc Med Nat Iasi. 2004 Apr-Jun;108(2):409-12. [PubMed:15688823]
  2. Kuster P, Taravella M, Gelinas M, Stepp P: Delivery of trifluridine to human cornea and aqueous using collagen shields. CLAO J. 1998 Apr;24(2):122-4. [PubMed:9571274]
  3. O'Brien WJ, Taylor JL: Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. Invest Ophthalmol Vis Sci. 1991 Aug;32(9):2455-61. [PubMed:1907950]
  4. Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. doi: 10.1080/07357900802087242. [PubMed:18798063]
  5. Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. [PubMed:16902987]
  6. Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. [PubMed:17179993]
External Links
Human Metabolome Database
HMDB14576
KEGG Drug
D00391
PubChem Compound
6256
PubChem Substance
46506192
ChemSpider
6020
BindingDB
50132298
ChEBI
75179
ChEMBL
CHEMBL1129
Therapeutic Targets Database
DAP000760
PharmGKB
PA451775
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Trifluridine
ATC Codes
S01AD02 — TrifluridineL01BC59 — Trifluridine, combinations
AHFS Codes
  • 52:04.20 — Antivirals
MSDS
Download (55.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
1CompletedTreatmentAdvanced Solid Tumors1
1Not Yet RecruitingTreatmentRectal Adenocarcinoma / Recurrent Rectal Carcinoma / Stage IV Rectal Cancer AJCC v7 / Stage IVA Rectal Cancer AJCC v7 / Stage IVB Rectal Cancer AJCC v71
1RecruitingTreatmentHepatic Metastases / Malignant Neoplasm of Colon / Rectal Carcinoma1
1RecruitingTreatmentPretreated Metastatic Colorectal Cancer1
1, 2Not Yet RecruitingTreatmentColorectal Cancers1
1, 2RecruitingTreatmentPreviously Treated Metastatic Colorectal Cancer1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
2Active Not RecruitingTreatmentRefractory, metastatic Colorectal cancer1
2Not Yet RecruitingTreatmentCholangiocarcinomas / Stage III Gallbladder Cancer AJCC V7 / Stage IIIA Gallbladder Cancer AJCC v7 / Stage IIIB Gallbladder Cancer AJCC v7 / Stage IV Gallbladder Cancer AJCC v7 / Stage IVA Gallbladder Cancer AJCC v7 / Stage IVB Gallbladder Cancer AJCC v71
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentSquamous Cell Lung Carcinoma1
Not AvailableCompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
  • Monarch pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral
SolutionOphthalmic10 mg/mL
Solution / dropsOphthalmic10 mg/mL
SolutionOphthalmic1 %
SolutionOphthalmic1 g/100mL
Prices
Unit descriptionCostUnit
Viroptic 1% Solution 7.5ml Bottle160.07USD bottle
Trifluridine 1% Solution 7.5ml Bottle153.4USD bottle
Trifluridine 1% eye drops19.69USD ml
Viroptic 1% eye drops18.63USD ml
Trifluridine 1 % opth soln15.21USD ml
Sandoz Trifluridine 1 % Solution3.41USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7799783No2006-12-162026-12-16Us
US5744475No1996-03-282016-03-28Us
US6479500No2000-03-162020-03-16Us
US9527833No2014-06-172034-06-17Us
USRE46284No2006-12-162026-12-16Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)186-189 °CPhysProp
water solubility1560 mg/LNot Available
logP-0.46HANSCH,C ET AL. (1995)
pKa7.95SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility6.69 mg/mLALOGPS
logP-0.45ALOGPS
logP-0.75ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)7.6ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area99.1 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity56.34 m3·mol-1ChemAxon
Polarizability23.07 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9636
Blood Brain Barrier+0.7348
Caco-2 permeable-0.8782
P-glycoprotein substrateNon-substrate0.7103
P-glycoprotein inhibitor INon-inhibitor0.8788
P-glycoprotein inhibitor IINon-inhibitor0.8078
Renal organic cation transporterNon-inhibitor0.9088
CYP450 2C9 substrateNon-substrate0.7706
CYP450 2D6 substrateNon-substrate0.8588
CYP450 3A4 substrateNon-substrate0.5276
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8903
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8652
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.7552
BiodegradationNot ready biodegradable0.9698
Rat acute toxicity2.4696 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9897
hERG inhibition (predictor II)Non-inhibitor0.7454
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Hydroxypyrimidines / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds / Primary alcohols / Organopnictogen compounds
show 5 more
Substituents
Pyrimidine 2'-deoxyribonucleoside / Pyrimidone / Hydroxypyrimidine / Hydropyrimidine / Pyrimidine / Tetrahydrofuran / Heteroaromatic compound / Secondary alcohol / Oxacycle / Azacycle
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, nucleoside analogue, pyrimidine 2'-deoxyribonucleoside (CHEBI:75179)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Thymidylate synthase activity
Specific Function
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name
TYMS
Uniprot ID
P04818
Uniprot Name
Thymidylate synthase
Molecular Weight
35715.65 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. De Clercq E: Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. [PubMed:15125867]
  3. Bijnsdorp IV, Kruyt FA, Fukushima M, Smid K, Gokoel S, Peters GJ: Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines. Cancer Sci. 2010 Feb;101(2):440-7. doi: 10.1111/j.1349-7006.2009.01375.x. Epub 2009 Sep 29. [PubMed:19886911]
  4. Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA: 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. 2010 May 15;126(10):2457-68. doi: 10.1002/ijc.24943. [PubMed:19816940]
  5. Bijnsdorp IV, Kruyt FA, Fukushima M, Peters GJ: Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703. doi: 10.1080/15257770802145017. [PubMed:18600528]
  6. Madeira VM, Antunes-Madeira MC: Chemical composition of sarcolemma isolated from rabbit skeletal muscle. Biochim Biophys Acta. 1973 Mar 16;298(2):230-8. [PubMed:4719131]
  7. Temmink OH, Hoogeland MF, Fukushima M, Peters GJ: Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells. Cancer Chemother Pharmacol. 2006 Jan;57(2):171-9. Epub 2005 Jul 12. [PubMed:16010590]
  8. Oberg B, Johansson NG: The relative merits and drawbacks of new nucleoside analogues with clinical potential. J Antimicrob Chemother. 1984 Aug;14 Suppl A:5-26. [PubMed:6436227]
  9. Temmink OH, Comijn EM, Fukushima M, Peters GJ: Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1491-4. [PubMed:15571283]
  10. Shintani M, Urano M, Takakuwa Y, Kuroda M, Kamoshida S: Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer. Oncol Rep. 2010 May;23(5):1345-50. [PubMed:20372850]
  11. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Kitazato K: Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model. Oncol Rep. 2004 Feb;11(2):381-7. [PubMed:14719072]
  12. Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. doi: 10.1080/07357900802087242. [PubMed:18798063]
  13. Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. [PubMed:16902987]
  14. Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. [PubMed:17179993]
  15. Bassler R, Buchwald W: [Experimental inflammation and fibrosis of the lung framework caused by ionizing rays. Light and electron microscopic studies]. Fortschr Geb Rontgenstr Nuklearmed. 1966 Feb;104(2):192-206. [PubMed:6010427]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Bijnsdorp IV, Kruyt FA, Fukushima M, Smid K, Gokoel S, Peters GJ: Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines. Cancer Sci. 2010 Feb;101(2):440-7. doi: 10.1111/j.1349-7006.2009.01375.x. Epub 2009 Sep 29. [PubMed:19886911]
  2. Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA: 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. 2010 May 15;126(10):2457-68. doi: 10.1002/ijc.24943. [PubMed:19816940]
  3. Bijnsdorp IV, Kruyt FA, Fukushima M, Peters GJ: Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703. doi: 10.1080/15257770802145017. [PubMed:18600528]
  4. Madeira VM, Antunes-Madeira MC: Chemical composition of sarcolemma isolated from rabbit skeletal muscle. Biochim Biophys Acta. 1973 Mar 16;298(2):230-8. [PubMed:4719131]
  5. Temmink OH, Hoogeland MF, Fukushima M, Peters GJ: Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells. Cancer Chemother Pharmacol. 2006 Jan;57(2):171-9. Epub 2005 Jul 12. [PubMed:16010590]
  6. Oberg B, Johansson NG: The relative merits and drawbacks of new nucleoside analogues with clinical potential. J Antimicrob Chemother. 1984 Aug;14 Suppl A:5-26. [PubMed:6436227]
  7. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Kitazato K: Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model. Oncol Rep. 2004 Feb;11(2):381-7. [PubMed:14719072]
  8. Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. doi: 10.1080/07357900802087242. [PubMed:18798063]
  9. Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. [PubMed:16902987]
  10. Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. [PubMed:17179993]
  11. Bassler R, Buchwald W: [Experimental inflammation and fibrosis of the lung framework caused by ionizing rays. Light and electron microscopic studies]. Fortschr Geb Rontgenstr Nuklearmed. 1966 Feb;104(2):192-206. [PubMed:6010427]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
TK1
Uniprot ID
P04183
Uniprot Name
Thymidine kinase, cytosolic
Molecular Weight
25468.455 Da
References
  1. Temmink OH, Comijn EM, Fukushima M, Peters GJ: Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1491-4. [PubMed:15571283]
  2. Shintani M, Urano M, Takakuwa Y, Kuroda M, Kamoshida S: Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer. Oncol Rep. 2010 May;23(5):1345-50. [PubMed:20372850]
  3. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Yokogawa T, Okabe H, Kitazato K: An optimal dosing schedule for a novel combination antimetabolite, TAS-102, based on its intracellular metabolism and its incorporation into DNA. Int J Mol Med. 2004 Feb;13(2):249-55. [PubMed:14719131]
  4. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Kitazato K: Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model. Oncol Rep. 2004 Feb;11(2):381-7. [PubMed:14719072]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transferase activity, transferring pentosyl groups
Specific Function
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in v...
Gene Name
TYMP
Uniprot ID
P19971
Uniprot Name
Thymidine phosphorylase
Molecular Weight
49954.965 Da
References
  1. Temmink OH, Comijn EM, Fukushima M, Peters GJ: Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1491-4. [PubMed:15571283]
  2. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Kitazato K: Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model. Oncol Rep. 2004 Feb;11(2):381-7. [PubMed:14719072]
  3. Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. doi: 10.1080/07357900802087242. [PubMed:18798063]
  4. Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. [PubMed:16902987]
  5. Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. [PubMed:17179993]
  6. Bassler R, Buchwald W: [Experimental inflammation and fibrosis of the lung framework caused by ionizing rays. Light and electron microscopic studies]. Fortschr Geb Rontgenstr Nuklearmed. 1966 Feb;104(2):192-206. [PubMed:6010427]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [PubMed:10945832]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2017 09:34