Doxifluridine

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Doxifluridine
Doxifluridine.svg
Clinical data
Other namesDoxyfluridine; doxifluridine; 5'-deoxy-5-fluorouridine; 5'-deoxy-5'-fluorouridine; 5'-fluoro-5'-deoxyuridine; 5'-dFUrd; 5'-DFUR; Furtulon; Ro 21-9738
Identifiers
  • 1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-methyloxolan-2-yl]-5-fluoropyrimidine-2,4-dione
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.019.491 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C9H11FN2O5
Molar mass 246.194 g·mol−1
3D model (JSmol)
  • C[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=C(C(=O)NC2=O)F)O)O
  • InChI=1S/C9H11FN2O5/c1-3-5(13)6(14)8(17-3)12-2-4(10)7(15)11-9(12)16/h2-3,5-6,8,13-14H,1H3,(H,11,15,16)/t3-,5-,6-,8-/m1/s1
  • Key:ZWAOHEXOSAUJHY-ZIYNGMLESA-N

Doxifluridine (5'-deoxy-5-fluorouridine) is a second generation nucleoside analog prodrug developed by Roche and used as a cytostatic agent in chemotherapy in several Asian countries including China and South Korea. [1] Doxifluridine is not FDA-approved for use in the USA. It is currently being evaluated in several clinical trials as a stand-alone or combination therapy treatment.

Contents

Biology

5-Fluorouracil (5-FU), the nucleobase of doxifluridine, is currently an FDA-approved antimetabolite. [2] 5-FU is normally administered intravenously to prevent its degradation by dihydropyrimidine dehydrogenase in the gut wall. Doxifluridine is a fluoropyrimidine derivative of 5-FU, thus a second-generation nucleoside prodrug. Doxifluridine was designed to improve oral bioavailability in order to avoid dihydropyrimidine dehydrogenase degradation in the digestive system. [3]

Within a cell, pyrimidine nucleoside phosphorylase or thymidine phosphorylase can metabolize doxifluridine into 5-FU. [4] [5] It is also a metabolite of capecitabine. [4] High levels of pyrimidine-nucleoside phosphorylase and thymidine phosphorylase are expressed in esophageal, breast, cervical, pancreatic, and hepatic cancers. [6] [7] Liberation of 5-FU is the active metabolite and leads to inhibition of DNA synthesis and cell death.

Side effects

High thymidine phosphorylase expression is also found in the human intestinal tract, resulting in dose-limiting toxicity (diarrhea) in some individuals. [8]

The most frequent adverse effects for doxifluridine were neurotoxicity and mucositis.[ citation needed ]

Brand names

Doxifluridine is sold under many brand names: [9]

Brand nameCompanyCountry
Didox [10] Shin Poong Pharm. Co., Ltd.South Korea
Doxyfluridine [9] Kwang Dong
Doxifluridine capMyungmoon Pharma Co. Ltd.
Ai Feng [9] HengruiChina and Japan
Doxifluridine [9] XinShiDai Pharmaceutical
Furtulon [9] Roche, Chugai
Ke Fu [9] Zhaohui
Ke Tuo [9] Southwest
Qi Nuo Bi Tong [9] Wanjie High-Tech
Shu Qi [9] Team
Tan Nuo [9] Xinchang Medicine & Chemical Co Ltd
Yi Di An [9] Pacific

Related Research Articles

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<span class="mw-page-title-main">Dihydropyrimidine dehydrogenase deficiency</span> Medical condition

Dihydropyrimidine dehydrogenase deficiency is an autosomal recessive metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

<span class="mw-page-title-main">Dihydropyrimidine dehydrogenase (NADP+)</span> Class of enzymes

In enzymology, a dihydropyrimidine dehydrogenase (NADP+) (EC 1.3.1.2) is an enzyme that catalyzes the chemical reaction

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TYMP is a gene that encodes for the enzyme thymidine phosphorylase. The TYMP gene is also known as ECGF1 and MNGIE due to its role in MNGIE syndrome.

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<span class="mw-page-title-main">Thymidine phosphorylase</span> Enzyme

Thymidine phosphorylase is an enzyme that is encoded by the TYMP gene and catalyzes the reaction:

<span class="mw-page-title-main">UPP1</span> Protein-coding gene in the species Homo sapiens

Uridine phosphorylase 1 is an enzyme that in humans is encoded by the UPP1 gene. It belongs to the uridine phosphorylase enzyme family.

<span class="mw-page-title-main">Sorivudine</span> Chemical compound

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<span class="mw-page-title-main">Tegafur</span> Chemical compound

Tegafur is a chemotherapeutic prodrug of 5-fluorouracil (5-FU) used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. When metabolised, it becomes 5-FU.

<span class="mw-page-title-main">Carmofur</span> Chemical compound

Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lipophilic-masked analog of 5-FU that can be administered orally.

<span class="mw-page-title-main">Sapacitabine</span> Chemical compound

Sapacitabine is a chemotherapeutic drug developed by US biotechnology firm Cyclacel currently undergoing clinical trials against leukemia.

<span class="mw-page-title-main">Trifluridine/tipiracil</span> Combination medication

Trifluridine/tipiracil (FTD–TPI), sold under the brand name Lonsurf, is a fixed-dose combination medication that is used as a third- or fourth-line treatment of metastatic colorectal cancer or gastric cancer, after chemotherapy and targeted therapeutics have failed. It is a combination of two active pharmaceutical ingredients: trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Tipiracil prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine.

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<span class="mw-page-title-main">Uridine triacetate</span> Chemical compound

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<span class="mw-page-title-main">Fluoropyrimidine</span> Index of chemical compounds with the same name

Fluoropyrimidines are a general class organic compounds in which the substituent(s) around a pyrimidine ring include at least one fluorine atom. The term "fluoropyrimidines" is often used more specifically to refer to the subset of this class that are antimetabolites and are used as anticancer medications, which include:

<span class="mw-page-title-main">Fluorodeoxyuridylate</span> Chemical compound

Fluorodeoxyuridylate, also known as FdUMP, 5-fluoro-2'-deoxyuridylate, and 5-fluoro-2'-deoxyuridine 5'-monophosphate, is a molecule formed in vivo from 5-fluorouracil and 5-fluorodeoxyuridine.

References

  1. ↑ "Doxifluridine". drugs.com.
  2. ↑ Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF (December 2016). "Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs". Chemical Reviews. 116 (23): 14379–14455. doi:10.1021/acs.chemrev.6b00209. PMC   7717319 . PMID   27960273.
  3. ↑ Schöffski P (February 2004). "The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors". Anti-Cancer Drugs. 15 (2): 85–106. doi:10.1097/00001813-200402000-00001. PMID   15075664.
  4. 1 2 Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, Ishitsuka H (February 1998). "Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts". Cancer Research. 58 (4): 685–690. PMID   9485021.
  5. ↑ "Definition of Doxifluridine". NCI Drug Dictionary. National Cancer Institute.
  6. ↑ Mori K, Hasegawa M, Nishida M, Toma H, Fukuda M, Kubota T, et al. (July 2000). "Expression levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in various human tumor tissues". International Journal of Oncology. 17 (1): 33–38. doi:10.3892/ijo.17.1.33. PMID   10853015.
  7. ↑ Ogata Y, Sasatomi T, Mori S, Matono K, Ishibashi N, Akagi Y, et al. (Jul 2007). "Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma". Anticancer Research. 27 (4C): 2605–2611. PMID   17695422.
  8. ↑ Lamont EB, Schilsky RL (September 1999). "The oral fluoropyrimidines in cancer chemotherapy". Clinical Cancer Research. 5 (9): 2289–2296. PMID   10499595.
  9. 1 2 3 4 5 6 7 8 9 10 11 "Medicine search - Doxifluridine". pillintrip.com. Retrieved 2022-02-12.
  10. ↑ Kim M, Ahn S, Son B, Lee J, Koh B, Sohn G, Lee S, Kim HJ (2017-02-23). "Oncologic Effect of Oral Fluorouracil in Hormone Receptor-Negative T1a Node-Negative Breast Cancer Patients". Journal of Breast Disease. 4 (2): 116–121. doi: 10.14449/jbd.2016.4.2.116 . ISSN   2288-5560.
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