Doxifluridine

Last updated
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 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 (5´-deoxy-5-fluorouridine) 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

Fluorouracil, sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for actinic keratosis, basal cell carcinoma, and skin warts.

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used in chemotherapy for cancer.

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

Capecitabine, sold under the brand name Xeloda among others, is a anticancer medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth.

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

Floxuridine is an oncology drug that belongs to the class known as antimetabolites. Specifically, floxuridine is a pyrimidine analog, classified as a deoxyuridine. The drug is usually administered via an artery, and most often used in the treatment of colorectal cancer. The quality of life and survival rates of individuals that receive continuous hepatic artery infusion of floxuridine for colorectal cancer metastases is significantly higher than control groups. Floxuridine can also be prescribed for the treatment of kidney and stomach cancers. In vitro uses of floxuridine include 5-minute treatments of fluorouracil, floxuridine, and mitomycin to increase cell proliferation in Tenon's capsule fibroblasts.

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

Brivudine is an antiviral drug used in the treatment of herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication of the target virus.

<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">Thymidylate synthase</span> Enzyme

Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage.

<span class="mw-page-title-main">Orotate phosphoribosyltransferase</span>

Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. In yeast and bacteria, orotate phosphoribosyltransferase is an independent enzyme with a unique gene coding for the protein, whereas in mammals and other multicellular organisms, the catalytic function is carried out by a domain of the bifunctional enzyme UMP synthase (UMPS).

<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

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

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.

Tegafur/uracil is a chemotherapy drug combination used in the treatment of cancer, primarily bowel cancer. It is also called UFT or UFUR.

<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

Sorivudine (INN), is a nucleoside analogue antiviral drug, marketed under trade names such as Usevir and Brovavir (BMS). It is used for the treatment of varicella zoster virus infections.

<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">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.

Tegafur/gimeracil/oteracil, sold under the brand name Teysuno among others is a fixed-dose combination medication used for the treatment of advanced gastric cancer when used in combination with cisplatin, and also for the treatment of head and neck cancer, colorectal cancer, non–small-cell lung, breast, pancreatic, and biliary tract cancers.

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

Uridine triacetate (INN), formerly known as vistonuridine, is an orally active tri-acetylated prodrug of uridine used:

<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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.