This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification
NameTegafur
Accession NumberDB09256
TypeSmall Molecule
GroupsApproved
Description

Tegafur (INN, BAN, USAN) is a prodrug of Fluorouracil (5-FU), an antineoplastic agent used as the treatment of various cancers such as stomach and colorectal cancers. It is used in combination therapies as an active chemotherapeutic agent in conjuction with Gimeracil and Oteracil, or along with Fluorouracil as Tegafur-uracil. Tegafur is usually given in combination with other drugs that enhance the bioavailability of the active drug or limit its toxicity. When metabolized to 5-FU, the drug mediates an antitumor activity by inhibiting thymidylate synthase (TS) to stop DNA replication in tumors. 5-FU is listed on the World Health Organization's List of Essential Medicines.

Structure
Thumb
Synonyms
1-(2-Tetrahydrofuryl)-5-fluorouracil
External IDs MJF-12264
Product Ingredients Not Available
ProductsNot Available
International Brands
NameCompany
Ai YiHengrui
ESUEEW AN TSawai Seiyaku
FimerLKM
FtorafurGrindeks
FurilLotus Pharmaceuticals
FutrafulTaiho
IcarusKoa Isei
LunacinSawai Seiyaku
NKS-1 TNippon Kayaku
Qi XingHualu Pharmaceutical
S-1Taiho
SterozineKotobuki Seiyaku
TefudexKorea United Pharma
TegacinPatron
TegracilShin Poong
TerofulKwang Dong
TS-1Toho Yakuhin
TS-ONETaiho
UFTMerck
UfurTTY
UnitoralKorea United Pharm
UtefosMylan
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
TeysunoCapsuleOralNordic Group Bv2011-03-14Not applicableEu
Categories
UNII1548R74NSZ
CAS number17902-23-7
WeightAverage: 200.169
Monoisotopic: 200.059720321
Chemical FormulaC8H9FN2O3
InChI KeyWFWLQNSHRPWKFK-UHFFFAOYSA-N
InChI
InChI=1S/C8H9FN2O3/c9-5-4-11(6-2-1-3-14-6)8(13)10-7(5)12/h4,6H,1-3H2,(H,10,12,13)
IUPAC Name
5-fluoro-1-(oxolan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
FC1=CN(C2CCCO2)C(=O)NC1=O
Pharmacology
Indication

Indicated for the treatment of cancer usually in combination with other biochemically modulating drugs.

Structured Indications
Pharmacodynamics

In a meta analysis, triple combination therapy consisting of tegafur, gimeracil and oteracil showed longer survival times and well tolerance in patients with advanced gastric cancer [3].

Mechanism of action

After administration into the body, tegafur is converted into the active antineoplastic metabolite, 5-fluorouracil (5-FU)

Related Articles
Absorption

Tegafur is rapidly and well absorbed into the systemic circulation, reaching the peak plasma concentration within 1 to 2 hours of administration.

Volume of distribution

The volume of distribution based on apparent volume of distribution and urinary excretion data of tegafur is 16 L/m^2 [4].

Protein binding

Tegafur is 52.3% bound to serum proteins and 5-FU is 18.4% protein bound [4, 5].

Metabolism

CYP2A6 is the major enzyme responsible for the conversion of tegafur to 5-FU [4]. 5-FU is metabolised by the liver enzyme dihydropyrimidine dehydrogenase (DPD).

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

Oral LD50 value in rat, mouse and dog are 930mg/kg, 775mg/kg, and 34mg/kg, respectively [MSDS]. Continuous exposure to tegafur may cause physical defects in the developing embryo (teratogenesis).

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*2A(A;A) / (A;G)G > A ADR Directly StudiedThe presence of this genotype in DPYD is associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*13(C;C) / (A;C)A > C ADR Directly StudiedThe presence of this genotype in DPYD is associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]---(A;A) / (A;T)T > A ADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*4(G;G) / (A:G)G > A ADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*5(G;G) / (A;G)A > G ADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*6(A;A) / (A;G)G > A ADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Dihydropyrimidine dehydrogenase [NADP(+)]DPYD*9A(C;C) / (C;T)T > C ADR Directly StudiedThe presence of this genotype in DPYD may be associated with an increased risk of drug-related toxicity from tegafur therapy. Details
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Tegafur.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Tegafur.Approved
AllopurinolThe therapeutic efficacy of Tegafur can be decreased when used in combination with Allopurinol.Approved
AmiodaroneThe serum concentration of the active metabolites of Tegafur can be reduced when Tegafur is used in combination with Amiodarone resulting in a loss in efficacy.Approved, Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Tegafur.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Tegafur.Approved
CimetidineThe serum concentration of the active metabolites of Tegafur can be increased when Tegafur is used in combination with Cimetidine.Approved
ClotrimazoleThe serum concentration of the active metabolites of Tegafur can be reduced when Tegafur is used in combination with Clotrimazole resulting in a loss in efficacy.Approved, Vet Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Tegafur.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Tegafur.Approved
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Tegafur.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Tegafur.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Tegafur.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Tegafur.Approved, Investigational
Ethyl biscoumacetateThe serum concentration of Ethyl biscoumacetate can be increased when it is combined with Tegafur.Withdrawn
FluindioneThe serum concentration of Fluindione can be increased when it is combined with Tegafur.Investigational
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Tegafur.Approved
LeucovorinThe risk or severity of adverse effects can be increased when Leucovorin is combined with Tegafur.Approved
LevoleucovorinThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Tegafur.Approved
MethotrexateThe risk or severity of adverse effects can be increased when Methotrexate is combined with Tegafur.Approved
MetronidazoleThe serum concentration of the active metabolites of Tegafur can be increased when Tegafur is used in combination with Metronidazole.Approved
NicotineThe serum concentration of the active metabolites of Tegafur can be reduced when Tegafur is used in combination with Nicotine resulting in a loss in efficacy.Approved
OleandrinAnvirzel may decrease the cardiotoxic activities of Tegafur.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Tegafur.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Tegafur.Approved, Vet Approved
PhenindioneThe serum concentration of Phenindione can be increased when it is combined with Tegafur.Approved
PhenprocoumonThe serum concentration of Phenprocoumon can be increased when it is combined with Tegafur.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Tegafur.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Tegafur.Approved, Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Tegafur.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Tsuburaya A, Morita S, Kodera Y, Kobayashi M, Shitara K, Yamaguchi K, Yoshikawa T, Yoshida K, Yoshino S, Sakamoto J: A randomized phase II trial to elucidate the efficacy of capecitabine plus cisplatin (XP) and S-1 plus cisplatin (SP) as a first-line treatment for advanced gastric cancer: XP ascertainment vs. SP randomized PII trial (XParTS II). BMC Cancer. 2012 Jul 23;12:307. doi: 10.1186/1471-2407-12-307. [PubMed:22824079 ]
  2. Ye JX, Liu AQ, Ge LY, Zhou SZ, Liang ZG: Effectiveness and safety profile of S-1-based chemotherapy compared with capecitabine-based chemotherapy for advanced gastric and colorectal cancer: A meta-analysis. Exp Ther Med. 2014 May;7(5):1271-1278. Epub 2014 Feb 24. [PubMed:24940424 ]
  3. Yang J, Zhou Y, Min K, Yao Q, Xu CN: S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: a meta-analysis. World J Gastroenterol. 2014 Sep 7;20(33):11886-93. doi: 10.3748/wjg.v20.i33.11886. [PubMed:25206296 ]
  4. European Medicines Agency (EMA): TEYSUNO (tegafur/gimeracil/oteracil) Summary of Product Characteristics [Link]
  5. UFT (uracil/tegafur) capsules_Product information [Link]
External Links
ATC CodesL01BC53 — Tegafur, combinationsL01BC03 — Tegafur
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (242 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentGastric Adenocarcinoma / Gastroesophageal Junction Adenocarcinoma1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentEsophageal Cancers1
1CompletedTreatmentMalignant Neoplasm of Stomach / Neoplasms, Gastrointestinal1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentStomach Neoplasms2
1CompletedTreatmentTumors1
1RecruitingTreatmentAdvanced Solid Tumors1
1RecruitingTreatmentDigestive Cancers1
1RecruitingTreatmentEsophageal Cancers1
1, 2CompletedTreatmentMalignant Neoplasm of Stomach2
1, 2RecruitingTreatmentAdenocarcinoma,Stomach / Esophagogastric Junction Adenocarcinoma1
1, 2SuspendedTreatmentMalignant Neoplasm of Pancreas1
1, 2Unknown StatusTreatmentRectal Carcinoma1
2Active Not RecruitingTreatmentAdvanced Pancreatic Cancer1
2Active Not RecruitingTreatmentBiliary Tract Neoplasms1
2Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
2Active Not RecruitingTreatmentSquamous Cell Carcinoma of Esophagus1
2CompletedDiagnosticMalignant Neoplasm of Stomach1
2CompletedTreatmentAdvanced Non-Small Cell Lung Cancer2
2CompletedTreatmentHepatocellular,Carcinoma2
2CompletedTreatmentLocally Advanced or Metastatic Pancreatic Cancer1
2CompletedTreatmentMalignant Neoplasm of Stomach6
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentSecondary Malignant Neoplasm of Pancreas1
2CompletedTreatmentStomach Neoplasms2
2Not Yet RecruitingTreatmentHepatocellular,Carcinoma1
2Not Yet RecruitingTreatmentMalignant Neoplasm of Stomach2
2Not Yet RecruitingTreatmentMetastatic Gastric Cancers1
2RecruitingTreatmentAdvanced or Metastatic Non-Small Cell Lung Cancer1
2RecruitingTreatmentBile Duct Neoplasms / Cancer of Unknown Primary Site / Gastrointestinal Cancers / Malignant Neoplasm of Pancreas1
2RecruitingTreatmentCarcinoma, Pancreatic1
2RecruitingTreatmentEsophageal Cancers / Radiotherapy / S-11
2RecruitingTreatmentEsophagus Cancer / Malignant Neoplasm of Colon / Malignant Neoplasm of Stomach / Rectum Cancer / Small Bowel Cancer1
2RecruitingTreatmentExtrapancreatic Neuroendocrine Tumor1
2RecruitingTreatmentGastroesophageal Junction Adenocarcinoma / Metastatic Gastric Adenocarcinoma1
2RecruitingTreatmentMalignant Neoplasm of Stomach3
2RecruitingTreatmentMetastatic Esophagogastric Adenocarcinoma1
2RecruitingTreatmentNasopharyngeal Carcinoma1
2RecruitingTreatmentNeoplasms, Head and Neck1
2RecruitingTreatmentPeritoneal Metastasis / Stomach Neoplasms1
2RecruitingTreatmentProgressive Neuroendocrine Tumors of pancreatic origin1
2RecruitingTreatmentRectal Carcinoma1
2RecruitingTreatmentSquamous Cell Carcinoma of Esophagus1
2SuspendedTreatmentMalignant Neoplasm of Stomach1
2TerminatedTreatmentMalignant Neoplasm of Pancreas1
2Unknown StatusTreatmentChemoradiotherapy, Adjuvant / Radiotherapy, Intensity-Modulated / Stomach Neoplasms1
2Unknown StatusTreatmentEsophageal Cancers / Malignant Neoplasm of Colon / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach1
2Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
2Unknown StatusTreatmentNeoplasms, Esophageal1
2, 3RecruitingTreatmentChemoradiation / Esophagogastric Junction Cancer / Esophagus Cancer / Radiotherapy; Complications1
2, 3RecruitingTreatmentMalignant Neoplasm of Stomach1
2, 3TerminatedTreatmentEsophageal Cancers1
2, 3TerminatedTreatmentMalignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentColorectal Cancers / Metastases1
3Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
3CompletedTreatmentCancer, Breast2
3CompletedTreatmentColorectal Cancers2
3CompletedTreatmentMalignant Neoplasm of Stomach2
3Enrolling by InvitationTreatmentMalignant Neoplasm of Stomach1
3Not Yet RecruitingTreatmentMalignant Neoplasm of Stomach1
3RecruitingTreatmentAdenocarcinomas / Chemoradiation / Gastrooesophageal Cancer / Locally Advanced Cancer / Stomach Neoplasms1
3RecruitingTreatmentChemoradiation / Esophageal Cancers1
3RecruitingTreatmentMalignant Neoplasm of Stomach2
3RecruitingTreatmentMalignant Neoplasm of Stomach / Stomach Neoplasms1
3RecruitingTreatmentNeoplasms, Esophageal1
3TerminatedTreatmentM0 / N0-2 / Rectal Carcinoma / Stage II/III / T3 or T4 (Only Anal Extension) Rectal Cancer1
3TerminatedTreatmentNeoplasms Metastasis / Neoplasms, Pancreatic1
4Not Yet RecruitingTreatmentNeoadjuvant Therapy / Neoplasms, Breast1
4Unknown StatusTreatmentHepatocellular,Carcinoma1
Not AvailableActive Not RecruitingNot AvailableStage IV Gastric Cancer With Metastasis1
Not AvailableActive Not RecruitingTreatmentCholangiocarcinomas1
Not AvailableRecruitingTreatmentMalignant Neoplasm of Pancreas1
Not AvailableUnknown StatusNot AvailableMalignant Neoplasm of Stomach1
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)339.8-343.4MSDS
water solubilityPartly miscibleMSDS
Predicted Properties
PropertyValueSource
Water Solubility14.0 mg/mLALOGPS
logP-0.09ALOGPS
logP0.024ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)8.08ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area58.64 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity44.5 m3·mol-1ChemAxon
Polarizability17.52 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-Bsplash10-00di-9010000000-09f17e43065fd7cafc97View in MoNA
GC-MSGC-MS Spectrum - CI-Bsplash10-0089-6900000000-0edac06a6aa07cfd4b9fView in MoNA
GC-MSGC-MS Spectrum - CI-Bsplash10-0udi-2190000000-6638249408dce3b6c1eeView in MoNA
GC-MSGC-MS Spectrum - CI-Bsplash10-014i-0090000000-dc47df1bb362c454d07dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassDiazines
Direct ParentHalopyrimidines
Alternative ParentsPyrimidones / Aryl fluorides / Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Tetrahydrofurans / Lactams / Ureas / Oxacyclic compounds / Azacyclic compounds
SubstituentsHalopyrimidine / Pyrimidone / Aryl fluoride / Aryl halide / Hydropyrimidine / Tetrahydrofuran / Vinylogous amide / Heteroaromatic compound / Urea / Lactam
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorspyrimidines, organohalogen compound (CHEBI:32188 )

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Uniprot Name:
Cytochrome P450 2A6
Molecular Weight:
56501.005 Da
References
  1. UFT (uracil/tegafur) capsules_Product information [Link]
Drug created on October 26, 2015 10:26 / Updated on September 01, 2017 15:53