Floxuridine

Antineoplastic antimetabolite CAS# 50-91-9

Floxuridine

Catalog No. BCC1187----Order now to get a substantial discount!

Product Name & Size Price Stock
Floxuridine:25mg $48.00 In stock
Floxuridine:50mg $82.00 In stock
Floxuridine:125mg $192.00 In stock
Floxuridine:250mg $336.00 In stock
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Chemical structure

Floxuridine

3D structure

Chemical Properties of Floxuridine

Cas No. 50-91-9 SDF Download SDF
PubChem ID 5790 Appearance Powder
Formula C9H11FN2O5 M.Wt 246.19
Type of Compound N/A Storage Desiccate at -20°C
Synonyms FdUrd
Solubility Soluble to 100 mM in water and to 100 mM in DMSO
Chemical Name 5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
SMILES C1C(C(OC1N2C=C(C(=O)NC2=O)F)CO)O
Standard InChIKey ODKNJVUHOIMIIZ-RRKCRQDMSA-N
Standard InChI InChI=1S/C9H11FN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Floxuridine

DescriptionAntineoplastic antimetabolite. Exhibits antiproliferative activity; inhibits thymidylate synthetase and disrupts DNA replication in human cells. Induces double-strand DNA breaks; activates ATR and ATM signaling pathways. Induces phosphorylation of Chk1 and Chk2 in OVCAR-8 and SKOV3ip ovarian cancer cell lines.

Floxuridine Dilution Calculator

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Floxuridine Molarity Calculator

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Preparing Stock Solutions of Floxuridine

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 4.0619 mL 20.3095 mL 40.619 mL 81.2381 mL 101.5476 mL
5 mM 0.8124 mL 4.0619 mL 8.1238 mL 16.2476 mL 20.3095 mL
10 mM 0.4062 mL 2.031 mL 4.0619 mL 8.1238 mL 10.1548 mL
50 mM 0.0812 mL 0.4062 mL 0.8124 mL 1.6248 mL 2.031 mL
100 mM 0.0406 mL 0.2031 mL 0.4062 mL 0.8124 mL 1.0155 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Floxuridine

Antineoplastic antimetabolite. Exhibits antiproliferative activity; inhibits thymidylate synthetase and disrupts DNA replication in human cells. Induces double-strand DNA breaks; activates ATR and ATM signaling pathways. Induces phosphorylation of Chk1 an

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References on Floxuridine

Glycogen Synthase Kinase 3 (GSK-3)-mediated Phosphorylation of Uracil N-Glycosylase 2 (UNG2) Facilitates the Repair of Floxuridine-induced DNA Lesions and Promotes Cell Survival.[Pubmed:27875297]

J Biol Chem. 2016 Dec 23;291(52):26875-26885.

Uracil N-glycosylase 2 (UNG2), the nuclear isoform of UNG, catalyzes the removal of uracil or 5-fluorouracil lesions that accumulate in DNA following treatment with the anticancer agents 5-fluorouracil and 5-fluorodeoxyuridine (Floxuridine), a 5-fluorouracil metabolite. By repairing these DNA lesions before they can cause cell death, UNG2 promotes cancer cell survival and is therefore critically involved in tumor resistance to these agents. However, the mechanisms by which UNG2 is regulated remain unclear. Several phosphorylation sites within the N-terminal regulatory domain of UNG2 have been identified, although the effects of these modifications on UNG2 function have not been fully explored, nor have the identities of the kinases involved been determined. Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr(60) and that Thr(60) phosphorylation requires a Ser(64) priming phosphorylation event. We also show that mutating Thr(60) or Ser(64) to Ala increases the half-life of UNG2, reduces the rate of in vitro uracil excision, and slows UNG2 dissociation from chromatin after DNA replication. Using an UNG2-deficient ovarian cancer cell line that is hypersensitive to Floxuridine, we show that GSK-3 phosphorylation facilitates UNG2-dependent repair of Floxuridine-induced DNA lesions and promotes tumor cell survival following exposure to this agent. These data suggest that GSK-3 regulates UNG2 and promotes DNA damage repair.

Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53.[Pubmed:27114909]

Genom Data. 2016 Mar 17;8:47-51.

Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF) properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC) harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of Floxuridine (FUdR) treated SW480 cells expressing mutant p53(R273H) (GEO#: GSE77533). We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.

Synergistic Combination Chemotherapy of Camptothecin and Floxuridine through Self-Assembly of Amphiphilic Drug-Drug Conjugate.[Pubmed:26497258]

Bioconjug Chem. 2015 Dec 16;26(12):2497-506.

Combination chemotherapy has been widely applied in cancer treatment; however, the cocktail administration of combination chemotherapy could cause the nonuniform biodistribution of anticancer agents, thus impairing the therapeutic efficacy. In the present study, to address this concern, we proposed a novel strategy of preparing self-assembled nanoparticles from amphiphilic drug-drug conjugate for synergistic combination chemotherapy. The conjugate was synthesized by two-step esterification of hydrophobic camptothecin (CPT) and hydrophilic Floxuridine (FUDR) through a linker compound. Because of its amphiphilic nature, the CPT-FUDR conjugate self-assembled into stable nanoparticles which could simultaneously release fixed dosage of the two drugs in cancer cells. In vitro studies demonstrated synergistic anticancer efficacy of the CPT-FUDR nanoparticles including improved cell apoptosis, varied cell cycle arrest, as well as effective inhibition of cancer cell proliferation.

Primary treatment of stage IV gestational trophoblastic neoplasia with floxuridine, dactinomycin, etoposide and vincristine (FAEV): A report based on our 10-year clinical experiences.[Pubmed:27426306]

Gynecol Oncol. 2016 Oct;143(1):68-72.

OBJECTIVE: To evaluate the efficacy and toxicity profile of Floxuridine, dactinomycin, etoposide and vincristine (FAEV) regimen as primary treatment in stage IV gestational trophoblastic neoplasia (GTN). METHODS: From 2004 to 2014, FAEV was given to 30 stage IV GTNs as the primary treatment (at least two cycles) in Peking Union Medical College Hospital. Remission/resistance/recurrence rate, the cause of treatment failure, and the toxicity profile were analyzed. RESULTS: A total of 190cycles of FAEV were administered to 30 patients; the median number of the cycles was 6 (range 3-11). The median follow up was 52.3months (range 8-120). Of all the patients received FAEV primarily, 24 achieved complete remission after only received FAEV, with no recurrence; 6 patients later switched to EMA-CO treatment due to FAEV resistance. Among the 6 patients, 2 died of progressive disease after multiple lines of chemotherapy, the other 4 achieved complete remission after second-line or third-line chemotherapy and 1 of them relapsed 15months later. FAEV was well tolerated. No one died from toxicity. Severe grade 4 neutropenia and thrombocytopenia were noted in 8 (26.7%) and 2 (6.7%) cases. No secondary malignancy was observed with follow-ups from 8 to120 months. Patients treated with FAEV showed good reproductive outcomes. CONCLUSIONS: FAEV regimen might be considered as an alternative to other chemotherapy regimen in the primary treatment of stage IV GTN, where it had a high rate of remission and a tolerable toxicity.

Poly(ADP-Ribose) polymerase inhibition synergizes with 5-fluorodeoxyuridine but not 5-fluorouracil in ovarian cancer cells.[Pubmed:21613406]

Cancer Res. 2011 Jul 15;71(14):4944-54.

5-Fluorouracil (5-FU) and 5-fluorodeoxyuridine (FdUrd, Floxuridine) have activity in multiple tumors, and both agents undergo intracellular processing to active metabolites that disrupt RNA and DNA metabolism. These agents cause imbalances in deoxynucleotide triphosphate levels and the accumulation of uracil and 5-FU in the genome, events that activate the ATR- and ATM-dependent checkpoint signaling pathways and the base excision repair (BER) pathway. Here, we assessed which DNA damage response and repair processes influence 5-FU and FdUrd toxicity in ovarian cancer cells. These studies revealed that disabling the ATM, ATR, or BER pathways using small inhibitory RNAs did not affect 5-FU cytotoxicity. In stark contrast, ATR and a functional BER pathway protected FdUrd-treated cells. Consistent with a role for the BER pathway, the poly(ADP-ribose) polymerase (PARP) inhibitors ABT-888 (veliparib) and AZD2281 (olaparib) markedly synergized with FdUrd but not with 5-FU in ovarian cancer cell lines. Furthermore, ABT-888 synergized with FdUrd far more effectively than other agents commonly used to treat ovarian cancer. These findings underscore differences in the cytotoxic mechanisms of 5-FU and FdUrd and suggest that combining FdUrd and PARP inhibitors may be an innovative therapeutic strategy for ovarian tumors.

Participation of DNA repair in the response to 5-fluorouracil.[Pubmed:18979208]

Cell Mol Life Sci. 2009 Mar;66(5):788-99.

The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments.

Human leukemic cells resistant to 5-fluoro-2'-deoxyuridine contain a thymidylate synthetase with lower affinity for nucleotides.[Pubmed:6220000]

J Biol Chem. 1983 Apr 10;258(7):4130-6.

A line of human lymphocytic leukemia cells (CCRF-CEM) has been obtained which is 140-fold resistant to the potent cell growth inhibitor 5-fluoro-2'-deoxyuridine (FdUrd). The cells were also 11-fold cross-resistant to 5-fluorouracil. In contrast to several previous studies involving FdUrd-resistant mouse cells, thymidylate synthetase levels were not substantially elevated in these FdUrd-resistant human leukemic cells. Thymidine kinase activity was also unchanged in the resistant cells, although the levels of 5-fluoro-2'-deoxyuridylate (FdUMP), the potent inhibitor of thymidylate synthetase, generated at equimolar doses of FdUrd were about 40% lower than in the sensitive cells. Studies of the kinetics of FdUMP binding to thymidylate synthetase isolated from the FdUrd-resistant cells disclosed a considerably higher dissociation constant (Kd = 1.0 X 10(-9) M) for the ternary covalent enzyme . FdUMP . 5,10-methylene tetrahydrofolate complex compared to the value obtained with enzyme from sensitive cells (Kd = 4.4 X 10(-11) M). The thymidylate synthetase from the FdUrd-resistant cells also showed 17-fold weaker binding of 2'-deoxyuridylate, even though the Km value for 2'-deoxyuridylate was 3-fold lower compared to the enzyme from FdUrd-sensitive cells. The turnover number of the altered enzyme was 1.8-fold higher than that for the normal enzyme but the rate constants for the release of FdUMP from the ternary complex, which is also an enzyme-catalyzed reaction, were identical for both enzymes. Electrophoresis of the radiolabeled ternary complexes on nondenaturing gels showed small but reproducible differences in migration rates. These results demonstrate that the mechanism of resistance to FdUrd in this cell line involves an alteration in the target enzyme, thymidylate synthetase, which causes it have a lower affinity for nucleotides.

Description

Floxuridine (5-Fluorouracil 2'-deoxyriboside) is a pyrimidine analog and known as an oncology antimetabolite. Floxuridine inhibits Poly(ADP-Ribose) polymerase and induces DNA damage by activating the ATM and ATR checkpoint signaling pathways in vitro. Floxuridine is a extreamly potent inhibitor for S. aureus infection and induces cell apoptosis. Floxuridine has antiviral effects against HSV and CMV.

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