Reaction: Capecitabine to 1 product

Reaction
Capecitabine
DB01101
5’-Deoxy-5-fluorocytidine (5'-DFCR)
DBMET03580
Reaction type
Amide Hydrolysis
Direction
Major circulating metabolite?
No
Spontaneous?
No
Activity
unknown
References
  1. Nies AT, Magdy T, Schwab M, Zanger UM: Role of ABC transporters in fluoropyrimidine-based chemotherapy response. Adv Cancer Res. 2015;125:217-43. doi: 10.1016/bs.acr.2014.10.007. Epub 2015 Jan 8. [Article]
  2. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [Article]
  3. Saif MW, Katirtzoglou NA, Syrigos KN: Capecitabine: an overview of the side effects and their management. Anticancer Drugs. 2008 Jun;19(5):447-64. doi: 10.1097/CAD.0b013e3282f945aa. [Article]
  4. Hishinuma E, Gutierrez Rico E, Hiratsuka M: In Vitro Assessment of Fluoropyrimidine-Metabolizing Enzymes: Dihydropyrimidine Dehydrogenase, Dihydropyrimidinase, and beta-Ureidopropionase. J Clin Med. 2020 Jul 22;9(8):2342. doi: 10.3390/jcm9082342. [Article]
  5. Krauss J, Bracher F: Pharmacokinetic Enhancers (Boosters)-Escort for Drugs against Degrading Enzymes and Beyond. Sci Pharm. 2018 Sep 27;86(4):E43. doi: 10.3390/scipharm86040043. [Article]
  6. Daher GC, Harris BE, Diasio RB: Metabolism of pyrimidine analogues and their nucleosides. Pharmacol Ther. 1990;48(2):189-222. doi: 10.1016/0163-7258(90)90080-l. [Article]
  7. Panczyk M: Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years. World J Gastroenterol. 2014 Aug 7;20(29):9775-827. doi: 10.3748/wjg.v20.i29.9775. [Article]
  8. Yablonski MJ, Pasek DA, Han BD, Jones ME, Traut TW: Intrinsic activity and stability of bifunctional human UMP synthase and its two separate catalytic domains, orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase. J Biol Chem. 1996 May 3;271(18):10704-8. doi: 10.1074/jbc.271.18.10704. [Article]
  9. 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 May;8(5):1037-44. doi: 10.1158/1535-7163.MCT-08-0716. Epub 2009 Apr 21. [Article]
  10. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5. [Article]
  11. Wen S, Wang X, Wang Y, Shen J, Pu J, Liang H, Chen C, Liu L, Dai P: Nucleoside diphosphate kinase 2 confers acquired 5-fluorouracil resistance in colorectal cancer cells. Artif Cells Nanomed Biotechnol. 2018;46(sup1):896-905. doi: 10.1080/21691401.2018.1439835. Epub 2018 Feb 23. [Article]
  12. Machon C, Catez F, Venezia ND, Vanhalle F, Guyot L, Vincent A, Garcia M, Roy B, Diaz JJ, Guitton J: Study of intracellular anabolism of 5-fluorouracil and incorporation in nucleic acids based on an LC-HRMS method. J Pharm Anal. 2021 Feb;11(1):77-87. doi: 10.1016/j.jpha.2020.04.001. Epub 2020 Apr 7. [Article]
  13. Wang Q, Liu X, Chen C, Chen J, Xu B, Chen L, Zhou J, Huang Y, Chen W, Teng R, Zhao W, Jin L, Shen J, Shen J, Yen Y, Wang L: A predictive signature for oxaliplatin and 5-fluorouracil based chemotherapy in locally advanced gastric cancer. Transl Oncol. 2021 Jan;14(1):100901. doi: 10.1016/j.tranon.2020.100901. Epub 2020 Oct 20. [Article]
  14. Liu X, Zhang H, Lai L, Wang X, Loera S, Xue L, He H, Zhang K, Hu S, Huang Y, Nelson RA, Zhou B, Zhou L, Chu P, Zhang S, Zheng S, Yen Y: Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers. Clin Sci (Lond). 2013 May;124(9):567-78. doi: 10.1042/CS20120240. [Article]
  15. Roosild TP, Castronovo S, Villoso A, Ziemba A, Pizzorno G: A novel structural mechanism for redox regulation of uridine phosphorylase 2 activity. J Struct Biol. 2011 Nov;176(2):229-37. doi: 10.1016/j.jsb.2011.08.002. Epub 2011 Aug 10. [Article]
  16. Biagioni A, Staderini F, Peri S, Versienti G, Schiavone N, Cianchi F, Papucci L, Magnelli L: 5-Fluorouracil Conversion Pathway Mutations in Gastric Cancer. Biology (Basel). 2020 Sep 2;9(9):265. doi: 10.3390/biology9090265. [Article]
  17. Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, Ando T, Yazaki N, Watanabe K, Haneda S, Shibata C, Sasaki I: 5-fu metabolism in cancer and orally-administrable 5-fu drugs. Cancers (Basel). 2010 Sep 17;2(3):1717-30. doi: 10.3390/cancers2031717. [Article]
  18. Che J, Pan L, Yang X, Liu Z, Huang L, Wen C, Lin A, Liu H: Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5-fluorouracil-based chemotherapy: A meta-analysis. Mol Clin Oncol. 2017 Dec;7(6):943-952. doi: 10.3892/mco.2017.1436. Epub 2017 Oct 3. [Article]
  19. Chalabi-Dchar M, Fenouil T, Machon C, Vincent A, Catez F, Marcel V, Mertani HC, Saurin JC, Bouvet P, Guitton J, Venezia ND, Diaz JJ: A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate. NAR Cancer. 2021 Aug 14;3(3):zcab032. doi: 10.1093/narcan/zcab032. eCollection 2021 Sep. [Article]
  20. FDA Approved Drug Products: XELODA® (capecitabine) tablets, for oral use Jan 2023 [Link]
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Enzymes
EnzymeKmVmaxRole
Liver carboxylesterase 1Not AvailableNot Availableconfirmed