Trifluridine

Identification

Summary

Trifluridine is a nucleoside metabolic inhibitor used to treat keratoconjunctivitis and epithelial keratitis caused by simplex virus, and as a part of chemotherapy for certain types of metastatic gastrointestinal cancers.

Brand Names
Lonsurf, Viroptic
Generic Name
Trifluridine
DrugBank Accession Number
DB00432
Background

Trifluridine is a fluorinated pyrimidine nucleoside that is structurally related to idoxuridine 1. It is an active antiviral agent in ophthalmic solutions used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. It displays effective antiviral activity against Herpes simplex virus type 1 and 2 1.

The combination product of trifluridine with tipiracil marketed as Lonsurf has been approved in Japan, the United States, and the European Union for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In the anticancer therapy, trifluridine acts as a thymidine-based nucleoside metabolic inhibitor that gets incorporated into DNA of cancer cells following cell uptake to aberrate DNA function during cell replication 10.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 296.1999
Monoisotopic: 296.062006087
Chemical Formula
C10H11F3N2O5
Synonyms
  • 5-(Trifluoromethyl)deoxyuridine
  • 5-Trifluoromethyl-2-deoxyuridine
  • F₃T
  • TFT
  • Trifluoromethyldeoxyuridine
  • Trifluorothymidine
  • Trifluorothymine deoxyriboside
  • Trifluridin
  • Trifluridina
  • Trifluridine
  • Trifluridinum

Pharmacology

Indication

As a standalone product, trifluridine is used for the ophthalmic treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.7

Trifluridine is also available as a combination product with tipiracil, which is indicated either alone or in combination with bevacizumab for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.8 This combination product is also used for adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma and were previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.8

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatMetastatic colorectal cancerRegimen in combination with: Bevacizumab (DB00112), Tipiracil (DB09343)••••••••••••••••••••••••• ••••••••• •••• ••••••••••••••••• ••••••••••• ••• ••••••••••• ••• ••••••••• •••• •••••••• •• ••••••••• •••••••• •••••••••• ••••••• •••• •••••••••••••••
Used in combination to treatMetastatic colorectal cancerCombination Product in combination with: Tipiracil (DB09343)••••••••••••••••••••••••••• ••••••• •••• •••••••••• ••• ••••••••• •••• •••••••• •• ••••••••• •••••••• •••••••• ••••••••• •••• ••••••••••••••••• ••••••••••• ••• ••••••••••••••••
Used in combination to treatMetastatic gastric cancersCombination Product in combination with: Tipiracil (DB09343)••••••••••••••••••••••••• ••••••••• •••• •• ••••••••••••••• •••••••• •••••••• •••••••••••••• ••••••••••••• •••••••••• ••••••• •••• •••••••••••••••• ••••••••••••• •••••••• •••••• •• •••••••••••••••• ••••••••••••• ••••• •• ••••• •• •••••••• •••••••••••••
Used in combination to treatMetastatic gastroesophageal junction adenocarcinomaCombination Product in combination with: Tipiracil (DB09343)••••••••••••••••••••••••• •••••••••••••• ••••••••••••• •••••••• ••••••••• •••• •• ••••••••••••••• •••••••• •••••••••• ••••••• •••• •••••••••••••••• ••••••••••••• ••••• •• ••••• •• •••••••• •••••••• •••••••• •••••• •• •••••••••••••••• ••••••••••••••••••
Treatment ofPrimary keratoconjunctivitis caused by herpes simplex virus type 1•••••••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Trifluridine exhibits an antiviral effect against herpes simplex virus, types 1 and 2 and vacciniavirus both in vitro and in vivo 1. Some strains of adenovirus that contribute to the pathology of keratoconjunctivitis were shown to be susceptible to trifluridine in vitro 1. While there is evidence from a study that cross-resistance may develop between trifluridine and idoxuridine or vidarabine, trifluridine was shown to effective in treating dendritic ulcers in patients with herpetic keratitis who are unresponsive to idoxuridine or vidarabine based on the results from masked comparative trials 1. In nonclinical studies, trifluridine/tipiracil hydrochloride demonstrated antitumour activity against both 5-fluorouracil (5-FU) sensitive and resistant colorectal cancer cell lines 10. The cytotoxic activity of trifluridine and tipiracil against several human tumour xenografts show high correlation with the amount of trifluridine incorporated into DNA, indicating that the primary mechanism of action of trifluridine involves the direct incorporation into the cancer cell DNA 10. Trifluridine and tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in mice Label.

In clinical studies comprised of patients with previously treated metastatic colorectal cancer, treatment of trifluridine in combination with tipiracil in addition to best supportive care over a 5- or 7-month period resulted in increased progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) compared to placebo 10. In an open-label study, administration of trifluridine at the recommended dosage in patients with advanced solid tumors had no clinically relevant effect on QT/QTc prolongation compared with placebo Label. Two out of 48 patients displayed had QTc greater than 500 msec and 1 of 42 patients (2.4%) had a QTc increase from baseline greater than 60 msec Label.

Mechanism of action

The mechanism of action of trifluridine as an antiviral agent has not been fully elucidated, but appears to involve the inhibition of viral replication. Trifluridine gets incorporated into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate. Trifluridine also mediates antineoplastic activities via this mechanism; following uptake into cancer cells, trifluridine is rapidly phosphorylated by thymidine kinase to its active monophosphate form 2. Subsequent phosphorylation produces trifluridine triphosphate 2, which is readily incorporated into the DNA of tumour cells in place of thymidine bases to perturb DNA function, DNA synthesis, and tumour cell proliferation Label. As trifluridine is subject to rapid degradation by TPase and readily metabolised by a first-pass effect following oral administration, tipiracil is added in the antineoplastic combination product as an inhibitor of TPase to increase the bioavailability of trifluridine 10. Trifluridine monophosphate also reversibly inhibits thymidylate synthetase (TS), an enzyme that is necessary for DNA synthesis and which levels are shown to be elevated different cancer cell lines 3. Up-regulation of the expression of the TS enzyme may also lead to the resistance to antineoplastic therapies, such as 5-fluorouracil (5-FU). [A35289 However, this inhibitory effect is not considered to be sufficient enough to fully contribute to the cytotoxicity in cancer cells. 2

TargetActionsOrganism
ADNA
other/unknown
Humans
AThymidylate synthase
inhibitor
Humans
Absorption

After oral administration of LONSURF with [14C]-trifluridine, at least 57% of the administered trifluridine was absorbed. Following a single dose of LONSURF (35 mg/m2) in patients with advanced solid tumors, the mean times to peak plasma concentrations (Tmax) of trifluridine was around 2 hours.9 Trifluridine area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) was approximately 3-fold higher and maximum concentration (Cmax) was approximately 2-fold higher after multiple dose administration (twice daily for 5 days a week with 2 days rest for 2 weeks followed by a 14-day rest, repeated every 4 weeks) than after single-dose administration.9

Following a single oral administration of LONSURF at 35 mg/m2 in patients with cancer, the mean time to peak plasma concentration (Tmax) of trifluridine was around 2 hours.8 For the ophthalmic formulation, systemic absorption appears to be negligible.7 A standardized high-fat, high-calorie meal decreased trifluridine Cmax by approximately 40% but did not change trifluridine AUC compared to those in a fasting state in patients with cancer following administration of a single dose of LONSURF 35 mg/m2.7

In a dose finding study (15 to 35 mg/m2 twice daily), the AUC from time 0 to 10 hours (AUC0-10) of trifluridine tended to increase more than expected based on the increase in dose.9

Volume of distribution

Following a single dose of LONSURF (35 mg/m2) in patients with advanced solid tumours, the apparent volume of distribution (Vd/F) for trifluridine was 21 L.9

Protein binding

In vitro findings suggest that the protein binding of trifluridine in human plasma is greater than 96%, where it is mainly bound to human serum albumin. Protein binding of trifluridine is independent of drug concentration and presence of tipiracil.8

Metabolism

Trifluridine is not metabolized by cytochrome P450 (CYP) enzymes. Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY). No other major metabolites were detected in plasma or urine.8 Other minor metabolites, such as 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea or 5-carboxyuraci, were also detected, but only at low or trace level in plasma and urine.4,9

Hover over products below to view reaction partners

Route of elimination

After single oral administration of LONSURF (60 mg) with [14C]-trifluridine, the total cumulative excretion of radioactivity was 60% of the administered dose. The majority of recovered radioactivity was eliminated into urine (55% of the dose) as FTY and trifluridine glucuronide isomers within 24 hours and the excretion into feces and expired air was <3% for both. The unchanged trifluridine was <3% of administered dose recovered in the urine and feces.8

Half-life

After administration of LONSURF 35 mg/m2, the mean elimination and steady-state half-life (t1/2) of trifluridine was 1.4 hours and 2.1 hours respectively.8 For the ophthalmic formulation, the half-life is significantly shorter, approximately only 12 minutes.7

Clearance

Following a single dose of LONSURF (35 mg/m2) in patients with advanced solid tumours, the oral clearance (CL/F) for trifluridine was 10.5 L/hr.9

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Intravenous LD50 in rat was 2946 mg/kg MSDS. Oral LD50 in rat and mouse were > 4379mg/kg MSDS. Overdosage via ocular instillation is unlikely. The highest dose of orally-administered Lonsurf, trifluridine in combination with tipiracil, administered in clinical studies was 180 mg/m^2 per day. The primary anticipated complication of an overdose is bone marrow suppression. There is no known antidote for trifluridine overdose: in case of an overdose, management should include customary therapeutic and supportive medical intervention aimed at correcting the presenting clinical manifestations and preventing their possible complications 10. Based on the findings from animal studies, trifluridine may cause fetal toxicity when administered to pregnant patients 10.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTrifluridine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Trifluridine is combined with Abatacept.
AceclofenacAceclofenac may decrease the excretion rate of Trifluridine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Trifluridine which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Trifluridine which could result in a higher serum level.
Food Interactions
  • Take with food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Thilol (Pharmex) / Triflumann (Dr. Gerhard Mann) / Triherpine (Medivis) / Virophta (Horus)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ViropticSolution1 g/100mLOphthalmicPhysicians Total Care, Inc.1980-04-102012-06-30US flag
ViropticSolution1 %OphthalmicBausch & Lomb Inc1987-12-31Not applicableCanada flag
ViropticSolution1 g/100mLOphthalmicPfizer Laboratories Div Pfizer Inc1980-04-102018-04-03US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-trifluridine Ophthalmic SolutionSolution1 %OphthalmicApotex CorporationNot applicableNot applicableCanada flag
Sandoz TrifluridineSolution1 %OphthalmicSandoz Canada Incorporated2004-01-232019-08-01Canada flag
TrifluridineSolution / drops10 mg/1mLOphthalmicHi-Tech Pharmacal Co., Inc.2017-07-28Not applicableUS flag
TrifluridineSolution1 g/100mLOphthalmicGreenstone LLC1980-04-102018-06-05US flag
TrifluridineSolution10 mg/1mLOphthalmicSandoz Inc2001-05-14Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
LONSURFTrifluridine (15 MG) + Tipiracil (6.14 MG)Tablet, film coatedOralLes Laboratoires Servier2016-09-22Not applicableItaly flag
LonsurfTrifluridine (15 mg/1) + Tipiracil hydrochloride (6.14 mg/1)Tablet, film coatedOralTaiho Pharmaceutical Co., Ltd.2015-09-22Not applicableUS flag
LonsurfTrifluridine (15 mg) + Tipiracil hydrochloride (6.14 mg)TabletOralTaiho Pharma Canada, Inc.2018-03-22Not applicableCanada flag
LonsurfTrifluridine (20 mg) + Tipiracil hydrochloride (8.19 mg)Tablet, film coatedOralLes Laboratoires Servier2016-09-08Not applicableEU flag
LonsurfTrifluridine (15 mg) + Tipiracil hydrochloride (6.14 mg)Tablet, film coatedOralLes Laboratoires Servier2016-09-08Not applicableEU flag

Categories

ATC Codes
L01BC59 — Trifluridine, combinationsS01AD02 — Trifluridine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Alkyl fluoride / Alkyl halide / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Hydroxypyrimidine / Organic nitrogen compound
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, nucleoside analogue, pyrimidine 2'-deoxyribonucleoside (CHEBI:75179)
Affected organisms
  • Human Herpes Virus

Chemical Identifiers

UNII
RMW9V5RW38
CAS number
70-00-8
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[C@H]1O[C@H](C[C@@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F

References

General References
  1. Carmine AA, Brogden RN, Heel RC, Speight TM, Avery GS: Trifluridine: a review of its antiviral activity and therapeutic use in the topical treatment of viral eye infections. Drugs. 1982 May;23(5):329-53. [Article]
  2. Burness CB, Duggan ST: Trifluridine/Tipiracil: A Review in Metastatic Colorectal Cancer. Drugs. 2016 Sep;76(14):1393-402. doi: 10.1007/s40265-016-0633-9. [Article]
  3. Matsuoka K, Nakagawa F, Kobunai T, Takechi T: Trifluridine/tipiracil overcomes the resistance of human gastric 5-fluorouracil-refractory cells with high thymidylate synthase expression. Oncotarget. 2018 Feb 5;9(17):13438-13450. doi: 10.18632/oncotarget.24412. eCollection 2018 Mar 2. [Article]
  4. Pavan-Langston D, Nelson DJ: Intraocular penetration of trifluridine. Am J Ophthalmol. 1979 Jun;87(6):814-8. [Article]
  5. Altmann S, Brandt CR, Murphy CJ, Patnaikuni R, Takla T, Toomey M, Nesbit B, McIntyre K, Covert J, Dubielzig R, Leatherberry G, Adkins E, Kodihalli S: Evaluation of therapeutic interventions for vaccinia virus keratitis. J Infect Dis. 2011 Mar 1;203(5):683-90. doi: 10.1093/infdis/jiq103. Epub 2011 Jan 28. [Article]
  6. FDA Approved Drug Products: LONSURF (trifluridine and tipiracil) tablets, for oral use [Link]
  7. FDA Approved Drug Products: TRIFLURIDINE solution for ophthalmic use [Link]
  8. FDA Approved Drug Products: LONSURF (trifluridine and tipiracil) tablets, for oral use (August 2023) [Link]
  9. EMA Product Information: LONSURF (trifluridine and tipiracil) tablets, for oral use [Link]
  10. Lonsurf Summary of Product Characteristics- European Medicines Agency - Europa EU [File]
  11. DailyMed Label: VIROPTIC® Ophthalmic Solution, 1% Sterile (trifluridine ophthalmic solution) [File]
Human Metabolome Database
HMDB0014576
KEGG Drug
D00391
PubChem Compound
6256
PubChem Substance
46506192
ChemSpider
6020
BindingDB
50132298
RxNav
10803
ChEBI
75179
ChEMBL
CHEMBL1129
ZINC
ZINC000003842753
Therapeutic Targets Database
DAP000760
PharmGKB
PA451775
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Trifluridine
FDA label
Download (490 KB)
MSDS
Download (50.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentColorectal Cancer3
3Active Not RecruitingTreatmentColorectal Neoplasms2
3Active Not RecruitingTreatmentMetastatic Colorectal Cancer (CRC)1
3CompletedTreatmentMetastatic Colorectal Cancer (CRC)1
3CompletedTreatmentRefractory, metastatic Colorectal cancer1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
  • Monarch pharmaceuticals inc
Packagers
  • Alcon Laboratories
  • DSM Corp.
  • Falcon Pharmaceuticals Ltd.
  • Monarch Pharmacy
  • Pharmedix
  • Physicians Total Care Inc.
  • Professional Compounding Centers America LLC
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
SolutionOphthalmic10 mg/1mL
Solution / dropsOphthalmic10 mg/1mL
OintmentTopical10 mg
Solution / dropsOphthalmic
SolutionConjunctival; Ophthalmic10 mg
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)Region
US7799783No2010-09-212026-12-16US flag
US5744475No1998-04-282016-03-28US flag
US6479500No2002-11-122020-03-16US flag
US9527833No2016-12-272034-06-17US flag
USRE46284No2017-01-242026-12-16US flag
US10456399No2019-10-292037-02-03US flag
US10457666No2019-10-292034-06-17US flag
US10960004No2021-03-302037-02-03US flag
US9943537No2018-04-172034-09-05US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)186-189PhysProp
water solubilitySolubleMSDS
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)8.5Chemaxon
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
Polarizability23.55 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-MSsplash10-002f-9070000000-5b0bc8f23d4e75143939
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4j-0090000000-ab5fcfff44302c75169b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-29274348cb9fb3333727
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01pk-7900000000-da39d725617ebd7d33f1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00n0-1970000000-c5de29c967465d2a8d4b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0r00-0590000000-9ea67cbe3b3d0426c103
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002f-7920000000-effccb223ba81d21c6ba
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-165.3156645
predicted
DarkChem Lite v0.1.0
[M-H]-165.69609
predicted
DeepCCS 1.0 (2019)
[M+H]+165.4855645
predicted
DarkChem Lite v0.1.0
[M+H]+168.09166
predicted
DeepCCS 1.0 (2019)
[M+Na]+165.4976645
predicted
DarkChem Lite v0.1.0
[M+Na]+174.31265
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other/unknown
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  2. De Clercq E: Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate profile was investigated in vitro using rat OAT1 expressed on Xenopus Laevis.
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. [Article]
  2. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine)....
Gene Name
SLC28A1
Uniprot ID
O00337
Uniprot Name
Sodium/nucleoside cotransporter 1
Molecular Weight
71583.18 Da
References
  1. Lonsurf Summary of Product Characteristics- European Medicines Agency - Europa EU [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Lonsurf Summary of Product Characteristics- European Medicines Agency - Europa EU [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Lonsurf Summary of Product Characteristics- European Medicines Agency - Europa EU [File]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48