Fluoropyrimidine activity (Homo sapiens)

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5, 10, 15, 17-19, 23...2DNA IncorporationCancer cellBasolateral membraneApical membraneReuptakeRNA IncorporationEffluxDrug resistanceLiver cell16FdUMPCES25-hydroxytegafur5-FUTDGCES1RRM1SMUG1FUMPDPYS5-dFCRERCC2CDAUMPSPPATXRCC3TYMPGGHTYMSUPB1SLC22A7FUDRFUTPFdUTPRRM25-dFURApoptosisUPP2Folate CycleTYMPTP535-FUdUMPFUPASLC29A1FPGSABCC4LeucovorinABCC4UPP1UPP2FUDPUPP15-fluorouracil (5-FU)TegafurCapecitabineUCK1ABCC5CYP2A6DHFUFUTPdTMPDPYDABCC3UCK2DHFRFdUMPMTHFRDihydrofolateABCG25,10-Methenyltetrahydrofolate5-FUFdUDPFURTK1DNA RepairFdUTPFBAL6, 20241113, 331, 21, 2617229351072748, 12, 143, 16, 25, 34, 36


Description

The main mechanism of 5-FU activation is conversion to fluorodeoxyuridine monophosphate (FdUMP) which inhibits the enzyme thymidylate synthase (TYMS), an important part of the folate-homocysteine cycle and purine and pyrimidine synthesis The conversion of 5-FU to FdUMP can occur via thymidylate phosphorylase (TYMP) to fluorodeoxyuridine (FUDR) and then by the action of thymidine kinase to FdUMP or indirectly via fluorouridine monophosphate (FUMP) or fluroridine (FUR) to fluorouridine diphosphate (FUDP) and then ribonucleotide reductase action to FdUDP and FdUMP. FUDP and FdUDP can also be converted to FUTP and FdUTP and incorporated into RNA and DNA respectively which also contributes to the pharmacodynamic actions of fluoropyrimidines. Sources: PharmGKB:Fluoropyrimidine Pharmacokinetics, PharmGKB:Fluoropyrimidine Pharmacodynamics, Wikipedia:Fluorouracil

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Bibliography

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  1. Marsh S; ''Thymidylate synthase pharmacogenetics.''; Invest New Drugs, 2005 PubMed Europe PMC Scholia
  2. Huang ZH, Hua D, Li LH, Zhu JD; ''Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy.''; J Cancer Res Clin Oncol, 2008 PubMed Europe PMC Scholia
  3. Peters EJ, Kraja AT, Lin SJ, Yen-Revollo JL, Marsh S, Province MA, McLeod HL; ''Association of thymidylate synthase variants with 5-fluorouracil cytotoxicity.''; Pharmacogenet Genomics, 2009 PubMed Europe PMC Scholia
  4. Hagmann W, Jesnowski R, Faissner R, Guo C, Löhr JM; ''ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells.''; Pancreatology, 2009 PubMed Europe PMC Scholia
  5. Yen-Revollo JL, Goldberg RM, McLeod HL; ''Can inhibiting dihydropyrimidine dehydrogenase limit hand-foot syndrome caused by fluoropyrimidines?''; Clin Cancer Res, 2008 PubMed Europe PMC Scholia
  6. Humeniuk R, Menon LG, Mishra PJ, Gorlick R, Sowers R, Rode W, Pizzorno G, Cheng YC, Kemeny N, Bertino JR, Banerjee D; ''Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance.''; Mol Cancer Ther, 2009 PubMed Europe PMC Scholia
  7. Longley DB, Harkin DP, Johnston PG; ''Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study.''; Neoplasma, 1976 PubMed Europe PMC Scholia
  8. Wang W, Cassidy J, O'Brien V, Ryan KM, Collie-Duguid E; ''Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells.''; Cancer Res, 2004 PubMed Europe PMC Scholia
  9. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H; ''Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.''; Eur J Cancer, 1998 PubMed Europe PMC Scholia
  10. Nordgard SH, Alnaes GI, Hihn B, Lingjaerde OC, Liestøl K, Tsalenko A, Sørlie T, Lønning PE, Børresen-Dale AL, Kristensen VN; ''Pathway based analysis of SNPs with relevance to 5-FU therapy: relation to intratumoral mRNA expression and survival.''; Int J Cancer, 2008 PubMed Europe PMC Scholia
  11. Diasio RB, Harris BE; ''Clinical pharmacology of 5-fluorouracil.''; Clin Pharmacokinet, 1989 PubMed Europe PMC Scholia
  12. De Angelis PM, Svendsrud DH, Kravik KL, Stokke T; ''Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery.''; Mol Cancer, 2006 PubMed Europe PMC Scholia
  13. Gmeiner WH; ''Novel chemical strategies for thymidylate synthase inhibition.''; Curr Med Chem, 2005 PubMed Europe PMC Scholia
  14. Behera RK, Nayak R; ''Expression profiling of nucleotide metabolism-related genes in human breast cancer cells after treatment with 5-fluorouracil.''; Cancer Invest, 2009 PubMed Europe PMC Scholia
  15. Yuan J, Lv H, Peng B, Wang C, Yu Y, He Z; ''Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer.''; Cancer Chemother Pharmacol, 2009 PubMed Europe PMC Scholia
  16. Huang MY, Fang WY, Lee SC, Cheng TL, Wang JY, Lin SR; ''ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study.''; BMC Cancer, 2008 PubMed Europe PMC Scholia
  17. Cao D, Russell RL, Zhang D, Leffert JJ, Pizzorno G; ''Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines.''; Cancer Res, 2002 PubMed Europe PMC Scholia
  18. Ruzzo A, Graziano F, Loupakis F, Santini D, Catalano V, Bisonni R, Ficarelli R, Fontana A, Andreoni F, Falcone A, Canestrari E, Tonini G, Mari D, Lippe P, Pizzagalli F, Schiavon G, Alessandroni P, Giustini L, Maltese P, Testa E, Menichetti ET, Magnani M; ''Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy.''; Pharmacogenomics J, 2008 PubMed Europe PMC Scholia
  19. Iacopetta B, Kawakami K, Watanabe T; ''Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup?''; Int J Clin Oncol, 2008 PubMed Europe PMC Scholia
  20. Karasawa H, Miura K, Fujibuchi W, Ishida K, Kaneko N, Kinouchi M, Okabe M, Ando T, Murata Y, Sasaki H, Takami K, Yamamura A, Shibata C, Sasaki I; ''Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells.''; Cancer Sci, 2009 PubMed Europe PMC Scholia
  21. Boyer J, Allen WL, McLean EG, Wilson PM, McCulla A, Moore S, Longley DB, Caldas C, Johnston PG; ''Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer.''; Cancer Res, 2006 PubMed Europe PMC Scholia
  22. Sobrero AF, Aschele C, Bertino JR; ''Fluorouracil in colorectal cancer--a tale of two drugs: implications for biochemical modulation.''; J Clin Oncol, 1997 PubMed Europe PMC Scholia
  23. An Q, Robins P, Lindahl T, Barnes DE; ''5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity.''; Cancer Res, 2007 PubMed Europe PMC Scholia
  24. Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AP, Mackey JR; ''Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.''; Gastroenterology, 2009 PubMed Europe PMC Scholia
  25. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P; ''MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
  26. van Kuilenburg AB, Meinsma R, Zonnenberg BA, Zoetekouw L, Baas F, Matsuda K, Tamaki N, van Gennip AH; ''Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity.''; Clin Cancer Res, 2003 PubMed Europe PMC Scholia
  27. Yuan JH, Cheng JQ, Jiang LY, Ji WD, Guo LF, Liu JJ, Xu XY, He JS, Wang XM, Zhuang ZX; ''Breast cancer resistance protein expression and 5-fluorouracil resistance.''; Biomed Environ Sci, 2008 PubMed Europe PMC Scholia
  28. Thomas HR, Ezzeldin HH, Guarcello V, Mattison LK, Fridley BL, Diasio RB; ''Genetic regulation of dihydropyrimidinase and its possible implication in altered uracil catabolism.''; Pharmacogenet Genomics, 2007 PubMed Europe PMC Scholia
  29. Jensen SA, Vainer B, Witton CJ, Jørgensen JT, Sørensen JB; ''Prognostic significance of numeric aberrations of genes for thymidylate synthase, thymidine phosphorylase and dihydrofolate reductase in colorectal cancer.''; Acta Oncol, 2008 PubMed Europe PMC Scholia
  30. De Mattia E, Toffoli G; ''C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation.''; Eur J Cancer, 2009 PubMed Europe PMC Scholia
  31. Kunz C, Focke F, Saito Y, Schuermann D, Lettieri T, Selfridge J, Schär P; ''Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil.''; PLoS Biol, 2009 PubMed Europe PMC Scholia
  32. Kidd EA, Yu J, Li X, Shannon WD, Watson MA, McLeod HL; ''Variance in the expression of 5-Fluorouracil pathway genes in colorectal cancer.''; Clin Cancer Res, 2005 PubMed Europe PMC Scholia
  33. Kobayashi Y, Ohshiro N, Sakai R, Ohbayashi M, Kohyama N, Yamamoto T; ''Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]).''; J Pharm Pharmacol, 2005 PubMed Europe PMC Scholia
  34. Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, Liu J, Etzel CJ, Amos CI, Huang M, Chiang SS, Milas L, Hittelman WN, Ajani JA; ''Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer.''; J Clin Oncol, 2006 PubMed Europe PMC Scholia
  35. Sakamoto E, Tsukioka S, Oie S, Kobunai T, Tsujimoto H, Sakamoto K, Okayama Y, Sugimoto Y, Oka T, Fukushima M; ''Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity.''; Biochem Biophys Res Commun, 2008 PubMed Europe PMC Scholia
  36. Gusella M, Padrini R; ''G>C SNP of thymidylate synthase with respect to colorectal cancer.''; Pharmacogenomics, 2007 PubMed Europe PMC Scholia
  37. Tsujie M, Nakamori S, Nakahira S, Takahashi Y, Hayashi N, Okami J, Nagano H, Dono K, Umeshita K, Sakon M, Monden M; ''Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer.''; Anticancer Res, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
126380view17:57, 25 April 2023EgonwLicense is CCZero
120496view07:21, 9 December 2021EgonwReplaced an old PubChem CID with the new one
117110view21:35, 17 May 2021EweitzModified title
108138view10:32, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
107122view14:20, 17 September 2019MaintBotChEBI identifier normalization
106698view13:09, 17 September 2019MaintBotHMDB identifier normalization
106419view22:00, 28 August 2019KhanspersModified description
105517view06:07, 8 August 2019KhanspersModified description
105516view06:06, 8 August 2019KhanspersUndo revision 105515 by [[Special:Contributions/Khanspers|Khanspers]] ([[User talk:Khanspers|Talk]])
105515view06:05, 8 August 2019KhanspersModified description
104914view19:24, 24 June 2019KhanspersReverted to version '02:10, 27 October 2017' by Khanspers
104806view19:56, 18 June 2019KhanspersModified description
95004view02:10, 27 October 2017EtaglobinTypo in last edit.
95003view02:07, 27 October 2017EtaglobinFixed dTMP HMDB identifier.
94711view05:11, 5 October 2017EgonwFixed character encoding.
94708view04:57, 5 October 2017EgonwReplaced the PubChem CID from the salt with that of the parent compound.
94193view14:32, 25 August 2017Mkutmonadded missing identifiers
92824view20:00, 8 July 2017AlexanderPicoChanged other FUTP to PubChem-compound
92823view19:55, 8 July 2017AlexanderPicoQuick edit to datanode annotation or property
91714view15:05, 29 March 2017DeSlUpdate with several identifiers (database references) added
84700view21:22, 15 March 2016KhanspersQuick edit to datanode annotation or property
82222view03:13, 16 September 2015AlexanderPicoungrouped pathway nodes for biopax conversion
80157view20:42, 14 May 2015KhanspersAdded mir29C targeting of TDG and correspondning reference
78516view10:29, 7 January 2015MaintBotadded missing graphIds
73314view18:31, 19 January 2014AaronCainechanged TYMS cofactor to 5,10 Methylenetetrahydrofolate from 5,10 methenyltetrahydrofolate
69925view19:50, 11 July 2013AlexanderPicoAdded datanode xrefs
59843view19:15, 8 March 2013KhanspersUpdated reference for dUMP
54388view21:16, 28 November 2012EgonwAdded the PubChem Compound ID for FUMP.
54353view11:50, 28 November 2012EveloSpecify description
54352view11:09, 28 November 2012EveloAdded Capecitabine ID from Chebi
54351view10:49, 28 November 2012EveloAdded (Chebi) IDs for 5FU itself
54350view10:35, 28 November 2012AnweshaPeriodical save, work in progress
47632view19:47, 31 March 2012AlexanderPicoadded db refs
46342view23:46, 18 January 2012KhanspersChanged cell shapes back to rounded rectangle
46341view22:39, 18 January 2012KhanspersRepalced rounded rectangles with rectangles
46305view17:39, 13 January 2012KhanspersAdded WikiPathways identifiers to pathway nodes
42640view21:09, 11 April 2011Khanspersfixed lines
41174view23:42, 1 March 2011MaintBotRemoved redundant pathway information and comments
39389view22:25, 19 November 2010AlexanderPicoOntology Term : 'hepatocyte' added !
39388view22:23, 19 November 2010AlexanderPicoOntology Term : 'drug pathway' added !
39387view22:23, 19 November 2010AlexanderPicoOntology Term : 'cancer' added !
39386view22:22, 19 November 2010AlexanderPicoupdated cells
38478view18:18, 17 September 2010AlexanderPicoModified description
38303view21:48, 30 August 2010AlexanderPicoReverted to version '14:42, 30 August 2010' by AlexanderPico
38302view21:47, 30 August 2010AlexanderPico
38301view21:42, 30 August 2010AlexanderPico
38291view07:56, 30 August 2010AlexanderPicoModified categories
38290view07:54, 30 August 2010AlexanderPico
38289view07:47, 30 August 2010AlexanderPicoadding literature refs
38288view07:22, 30 August 2010AlexanderPicoModified description

External references

DataNodes

View all...
NameTypeDatabase referenceComment
5,10-MethenyltetrahydrofolateMetaboliteHMDB01354 (HMDB)
5-FUMetabolite46345 (ChEBI)
5-dFCRMetabolite
5-dFURMetabolite
5-fluorouracil (5-FU)Metabolite46345 (ChEBI)
5-hydroxytegafurMetabolite
ABCC3GeneProduct8714 (Entrez Gene)
ABCC4GeneProduct10257 (Entrez Gene)
ABCC5GeneProduct10057 (Entrez Gene)
ABCG2GeneProduct9429 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
CDAGeneProduct978 (Entrez Gene)
CES1GeneProduct1066 (Entrez Gene)
CES2GeneProduct8824 (Entrez Gene)
CYP2A6GeneProduct1548 (Entrez Gene)
CapecitabineMetabolite
DHFRGeneProduct1719 (Entrez Gene)
DHFUMetabolite
DNA RepairPathwayWP1805 (WikiPathways)
DPYDGeneProduct1806 (Entrez Gene)
DPYSGeneProduct1807 (Entrez Gene)
DihydrofolateMetaboliteHMDB01056 (HMDB)
ERCC2GeneProduct2068 (Entrez Gene)
FBALMetabolite
FPGSGeneProduct2356 (Entrez Gene)
FUDPMetabolite
FUDRMetabolite
FUMPMetabolite
FUPAMetabolite
FURMetabolite
FUTPMetabolite
FdUDPMetabolite
FdUMPMetabolite
FdUTPMetabolite
Folate CyclePathway
GGHGeneProduct8836 (Entrez Gene)
LeucovorinMetabolite
MTHFRGeneProduct4524 (Entrez Gene)
PPATGeneProduct5471 (Entrez Gene)
RRM1GeneProduct6240 (Entrez Gene)
RRM2GeneProduct6241 (Entrez Gene)
SLC22A7GeneProduct10864 (Entrez Gene)
SLC29A1GeneProduct2030 (Entrez Gene)
SMUG1GeneProduct23583 (Entrez Gene)
TDGGeneProduct6996 (Entrez Gene)
TK1GeneProduct7083 (Entrez Gene)
TP53GeneProduct7157 (Entrez Gene)
TYMPGeneProduct1890 (Entrez Gene)
TYMSGeneProduct7298 (Entrez Gene)
TegafurMetabolite
UCK1GeneProduct83549 (Entrez Gene)
UCK2GeneProduct7371 (Entrez Gene)
UMPSGeneProduct7372 (Entrez Gene)
UPB1GeneProduct51733 (Entrez Gene)
UPP1GeneProduct7378 (Entrez Gene)
UPP2GeneProduct151531 (Entrez Gene)
XRCC3GeneProduct7517 (Entrez Gene)
dTMPMetaboliteHMDB01056 (HMDB)
dUMPMetaboliteHMDB01056 (HMDB)

Annotated Interactions

No annotated interactions

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