# Tegafur

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Tegafur
> Markdown URL: https://mediated.wiki/source/Tegafur.md
> Source: https://en.wikipedia.org/wiki/Tegafur
> Source revision: 1346950137
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 470478587
| IUPAC_name = (''RS'')-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1''H'',3''H'')-dione
| image = Tegafur.svg
| image_class = skin-invert-image
| alt = Skeletal formula of tegafur
| width = 150
| image2 = Tegafur-3D-balls.png
| image_class2 = bg-transparent
| alt2 = Ball-and-stick model of the tegafur molecule
| width2 = 125
<!--Clinical data-->
| tradename =  
| Drugs.com = {{drugs.com|international|tegafur}}
| pregnancy_AU = D
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category =  
| licence_EU = yes
| legal_AU = S4
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = POM
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| bioavailability =  
| protein_bound =  
| metabolism =  
| elimination_half-life = 3.9-11 hours
| excretion =  
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 17902-23-7
| ATC_prefix = L01
| ATC_suffix = BC03
| ATC_supplemental = {{ATC|L01|BC53}}

| PubChem = 288216
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB09256
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 254191
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1548R74NSZ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01244
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 20883
<!--Chemical data-->
| chemical_formula =
| C=8 | H=9 | F=1 | N=2 | O=3
| smiles = FC=1C(=O)NC(=O)N(C=1)[C@@H]2OCCC2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)/t6-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WFWLQNSHRPWKFK-ZCFIWIBFSA-N
| synonyms = <small>5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione</small>
}}
<!-- Definition and medical uses -->
'''Tegafur''' is a [chemotherapeutic](/source/chemotherapeutic) [prodrug](/source/prodrug) of [5-fluorouracil](/source/5-fluorouracil) (5-FU) used in the treatment of cancers. It is a component of the combination drug [tegafur/uracil](/source/tegafur%2Furacil). When metabolised, it becomes 5-FU.<ref>{{cite journal | vauthors = El Sayed YM, Sadée W | title = Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes | journal = Cancer Research | volume = 43 | issue = 9 | pages = 4039–4044 | date = September 1983 | pmid = 6409396 }}</ref>

<!-- Society and culture -->
It was patented in 1967 and approved for medical use in 1972.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=511 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA511 |language=en}}</ref>

==Medical uses==
As a prodrug to 5-FU it is used in the treatment of the following cancers:<ref name = MD>{{cite web|title=Martindale: The Complete Drug Reference |publisher=Pharmaceutical Press |date=14 November 2011 |access-date=12 February 2014 |url= http://www.medicinescomplete.com/mc/martindale/current/1866-m.htm| veditors = Sweetman S }}</ref>
* [Stomach](/source/Stomach_cancer) (when combined with [gimeracil and oteracil](/source/Tegafur%2Fgimeracil%2Foteracil))
* [Breast](/source/Breast_cancer) (with uracil)
* [Gallbladder](/source/Gallbladder_cancer)
* [Lung](/source/Lung_cancer) (specifically adenocarcinoma, typically with uracil)
* [Colorectal](/source/Colorectal_cancer) (usually when combined with gimeracil and oteracil)
* [Head and neck](/source/Head_and_neck_cancer)
* [Liver](/source/Liver_cancer) (with uracil)<ref>{{cite journal | vauthors = Ishikawa T | title = Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma | journal = World Journal of Gastroenterology | volume = 14 | issue = 18 | pages = 2797–2801 | date = May 2008 | pmid = 18473401 | pmc = 2710718 | doi = 10.3748/wjg.14.2797 | doi-access = free }}</ref>
* [Pancreatic](/source/Pancreatic_cancer)

It is often given in combination with drugs that alter its bioavailability and toxicity such as gimeracil, oteracil or uracil.<ref name = MD/> These agents achieve this by inhibiting the enzyme [dihydropyrimidine dehydrogenase](/source/dihydropyrimidine_dehydrogenase) (uracil/gimeracil) or [orotate phosphoribosyltransferase](/source/orotate_phosphoribosyltransferase) (oteracil).<ref name = MD/>

==Adverse effects==
The major side effects of tegafur are similar to fluorouracil and include myelosuppression, central neurotoxicity and gastrointestinal toxicity (especially diarrhoea).<ref name = MD/> Gastrointestinal toxicity is the dose-limiting side effect of tegafur.<ref name = MD/> Central neurotoxicity is more common with tegafur than with fluorouracil.<ref name = MD/>

===Pharmacogenetics===

The [dihydropyrimidine dehydrogenase](/source/dihydropyrimidine_dehydrogenase) (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes [5-fluorouracil](/source/5-fluorouracil), [capecitabine](/source/capecitabine), and tegafur.<ref name="pmid23988873">{{cite journal | vauthors = Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M | title = Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 6 | pages = 640–645 | date = December 2013 | pmid = 23988873 | pmc = 3831181 | doi = 10.1038/clpt.2013.172 }}</ref> [Genetic variation](/source/Genetic_variation)s within the DPD gene (''DPYD'') can lead to reduced or absent DPD activity, and individuals who are [heterozygous](/source/heterozygous) or [homozygous](/source/homozygous) for these variations may have partial or complete [DPD deficiency](/source/DPD_deficiency); an estimated 0.2% of individuals have complete [DPD deficiency](/source/DPD_deficiency).<ref name="pmid23988873"/><ref name="pmid21919607">{{cite journal | vauthors = Amstutz U, Froehlich TK, Largiadèr CR | title = Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity | journal = Pharmacogenomics | volume = 12 | issue = 9 | pages = 1321–1336 | date = September 2011 | pmid = 21919607 | doi = 10.2217/pgs.11.72 }}</ref> Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include [myelosuppression](/source/myelosuppression), [neurotoxicity](/source/neurotoxicity) and [hand-foot syndrome](/source/hand-foot_syndrome).<ref name="pmid23988873"/><ref name="pmid21919607"/>

==Mechanism of action==
It is a prodrug to 5-FU, which is a [thymidylate synthase](/source/thymidylate_synthase) inhibitor.<ref name = MD/>

==Pharmacokinetics==
It is metabolised to 5-FU by [CYP2A6](/source/CYP2A6).<ref>{{cite journal | vauthors = Nakayama T, Noguchi S | title = Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan | journal = The Oncologist | volume = 15 | issue = 1 | pages = 26–36 | date = January 2010 | pmid = 20080863 | pmc = 3227888 | doi = 10.1634/theoncologist.2009-0255 }}</ref><ref>{{cite journal | vauthors = Matt P, van Zwieten-Boot B, Calvo Rojas G, Ter Hofstede H, Garcia-Carbonero R, Camarero J, Abadie E, Pignatti F | display-authors = 6 | title = The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the treatment of advanced gastric cancer when given in combination with cisplatin: summary of the Scientific Assessment of the Committee for medicinal products for human use (CHMP) | journal = The Oncologist | volume = 16 | issue = 10 | pages = 1451–1457 | date = October 2011 | pmid = 21963999 | pmc = 3228070 | doi = 10.1634/theoncologist.2011-0224 }}</ref>

== Interactive pathway map ==
{{FluoropyrimidineActivity WP1601|highlight=Tegafur}}

== See also ==
* [Tegafur/uracil](/source/Tegafur%2Furacil)
* [Tegafur/gimeracil/oteracil](/source/Tegafur%2Fgimeracil%2Foteracil)

== References ==
{{reflist}}

{{Chemotherapeutic agents}}

Category:Organofluorides
Category:Prodrugs
Category:Uracil derivatives
Category:Pyrimidine antagonists
Category:Tetrahydrofurans
Category:Fluoropyrimidines
Category:Drugs in the Soviet Union

---
Adapted from the Wikipedia article [Tegafur](https://en.wikipedia.org/wiki/Tegafur) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Tegafur?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.