Floxuridine | CAS#50-91-9 | antimetabolite agent

MedKoo Cat#: 100360 | Name: Floxuridine

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Floxuridine is a fluorinated pyrimidine monophosphate analogue of 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) with antineoplastic activity. As an antimetabolite, floxuridine inhibits thymidylate synthetase, resulting in disruption of DNA synthesis and cytotoxicity. This agent is also metabolized to fluorouracil and other metabolites that can be incorporated into RNA and inhibit the utilization of preformed uracil in RNA synthesis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Chemical Structure

Floxuridine

CAS#50-91-9

Theoretical Analysis

MedKoo Cat#: 100360

Name: Floxuridine

CAS#: 50-91-9

Chemical Formula: C9H11FN2O5

Exact Mass: 246.0652

Molecular Weight: 246.19

Elemental Analysis: C, 43.91; H, 4.50; F, 7.72; N, 11.38; O, 32.49

Price and Availability

Size	Price	Availability
50mg	USD 90.00	Ready to ship
100mg	USD 150.00	Ready to ship
200mg	USD 225.00	Ready to ship
500mg	USD 450.00	Ready to ship
1g	USD 750.00	Ready to ship
2g	USD 1,250.00	Ready to ship

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Related CAS #

No Data

Synonym

FdUrD; floxuridin; fluorodeoxyuridine; fluorouridine deoxyribose; fluoruridine deoxyribose. FUDF. 5FUDR; FDUR; FUdR. WR138720.

IUPAC/Chemical Name

5-fluoro-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione

InChi Key

ODKNJVUHOIMIIZ-RRKCRQDMSA-N

InChi Code

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

SMILES Code

O=C1NC(C(F)=CN1[C@@H]2O[C@H](CO)[C@@H](O)C2)=O

Appearance

White powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in water (50 mg/ml), alcohol (1:12), isopropyl alcohol (1:43), methanol (1:7), aqueous buffers, acetone, DMSO (49 mg/ml) at 25 Â°C, and ethanol (10 mg/ml) at 25 Â°C. Insoluble in ether, benzene, and chloroform.

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

DRUG DESCRIPTION Floxuridine for Injection USP, an antineoplastic antimetabolite, is available as a sterile, nonpyrogenic, lyophilized powder for reconstitution. Each vial contains 500 mg of floxuridine which is to be reconstituted with 5 mL of sterile water for injection. An appropriate amount of reconstituted solution is then diluted with a parenteral solution for intra-arterial infusion. Floxuridine is a fluorinated pyrimidine. Chemically, floxuridine is 2'-Deoxy-5-fluorouridine, with a molecular formula of C9H11FN2O5. It is a white to off-white odorless solid which is freely soluble in water. The 2% aqueous solution has a pH of between 4.0 and 5.5. The molecular weight of floxuridine is 246.20. CLINICAL PHARMACOLOGY When floxuridine is given by rapid intra-arterial injection it is apparently rapidly catabolized to 5-fluorouracil. Thus, rapid injection of floxuridine produces the same toxic and antimetabolic effects as does 5-fluorouracil. The primary effect is to interfere with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibit the formation of ribonucleic acid (RNA). However, when floxuridine is given by continuous intraarterial infusion its direct anabolism to floxuridine-monophosphate is enhanced, thus increasing the inhibition of DNA. Floxuridine is metabolized in the liver. The drug is excreted intact and as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid and α-fluoro-β-alanine in the urine; it is also expired as respiratory carbon dioxide. Pharmacokinetic data on intra-arterial infusion of floxuridine are not available.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YYP31029

QC Data

View QC data: current batch, Lot#YYP31029

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Floxuridine (5-Fluorouracil 2'-deoxyriboside) is a pyrimidine analog and an oncology antimetabolite, that inhibits Poly(ADP-Ribose) polymerase and induces DNA damage

In vitro activity:

The metabolic stability of floxuridine and its amino ester prodrugs was assessed using thymidine phosphorylase. The results shown in Table 33 indicate that floxuridine was rapidly degraded to the less active metabolite, 5-fluorouracil, by thymidine phosphorylase. The amino acid ester prodrugs of floxuridine were found to be quite resistant to degradation by thymidine phosphorylase. Prodrugs containing the glycyl moiety, 5-l-glycyl, 5-l-leucyl-l-glycyl, 5-l-glycyl-l-leucyl, 5-l-phenylalanyl-l-glycyl, and 5-l-isoleucyl-l-glycyl floxuridine were 20- to 40-fold more stable than floxuridine to degradation by thymidine phosphorylase. The half-lives of 5-lphenylalanyl-floxuridine, 5-l-isoleucyl-floxuridine, 5-l-valyl-l-phenylalanyl-floxuridine, and 5-l-phenylalanyl-l-tyrosyl-floxuridine were in excess of 500 min reflecting their superior resistance to metabolic degradation by thymidine phosphorylase. The results are consistent with the stability of the prodrugs in buffer systems. With the exception of 5-l-leucyl and 5-l-glycyl dipeptide analogs with Caco-2 cells, all dipeptide prodrugs of floxuridine exhibited 2- to 14-fold higher affinity for oligopeptide transporters than the corresponding 5-l-monoester prodrug. The cell proliferation studies in the pancreatic duct cancer cell lines confirmed the enhanced potency of the amino acid ester prodrugs compared to parent floxuridine. The lack of potency enhancement of 5-d-valyl-floxuridine in Capan-2 cells compared to floxuridine suggests that activation of the prodrugs to the parent is essential for cytotoxic action and is enzyme-specific. Mol Pharm. 2008 Oct 6; 5(5): 717–727. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659690/

In vivo activity:

Floxuridine (5'-fluorodeoxyuridine, FUdR) acts as an inhibitor of DNA replication by binding to thymidylate synthase and is widely used to treat colorectal cancer. FUdR is also frequently used in research on aging in C. elegans since by blocking reproduction it allows maintenance of synchronous nematode populations. Here we examine age-specific effects of exposure to 50 μM FUdR on pathology and mortality. We report that initiating exposure to FUdR at late development or early adulthood reduces lifespan but later initiation increases it. Moreover, earlier initiation leads to enhancement of senescent intestinal atrophy, but amelioration of several other senescent pathologies (pharyngeal degeneration and uterine tumors). These results provide further evidence of the complex effects of FUdR on aging in C. elegans, and therefore support the argue against its routine use in studies of nematode aging due to its possible confounding effects. However, they also illustrate how effects of FUdR on aging are interesting in their own right. Biochem Biophys Res Commun. 2019 Feb 12;509(3):694-699. https://pubmed.ncbi.nlm.nih.gov/30611569/

	Solvent	mg/mL	mM
Solubility
	DMSO	58.0	237.36
	H20	41.0	167.46

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 246.19 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Chirio D, Peira E, Battaglia L, Ferrara B, Barge A, Sapino S, Giordano S, Dianzani C, Gallarate M. Lipophilic Prodrug of Floxuridine Loaded into Solid Lipid Nanoparticles: In Vitro Cytotoxicity Studies on Different Human Cancer Cell Lines. J Nanosci Nanotechnol. 2018 Jan 1;18(1):556-563. doi: 10.1166/jnn.2018.13964. PMID: 29768881. 2. Tsume Y, Hilfinger JM, Amidon GL. Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm. 2008 Sep-Oct;5(5):717-27. doi: 10.1021/mp800008c. Epub 2008 Jul 25. PMID: 18652477; PMCID: PMC2659690. 3.Tardi PG, Gallagher RC, Johnstone S, Harasym N, Webb M, Bally MB, Mayer LD. Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo. Biochim Biophys Acta. 2007 Mar;1768(3):678-87. doi: 10.1016/j.bbamem.2006.11.014. Epub 2006 Dec 6. PMID: 17208196. 4. Wang H, Zhao Y, Zhang Z. Age-dependent effects of floxuridine (FUdR) on senescent pathology and mortality in the nematode Caenorhabditis elegans. Biochem Biophys Res Commun. 2019 Feb 12;509(3):694-699. doi: 10.1016/j.bbrc.2018.12.161. Epub 2019 Jan 3. PMID: 30611569

In vitro protocol:

In vivo protocol:

1. Tardi PG, Gallagher RC, Johnstone S, Harasym N, Webb M, Bally MB, Mayer LD. Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo. Biochim Biophys Acta. 2007 Mar;1768(3):678-87. doi: 10.1016/j.bbamem.2006.11.014. Epub 2006 Dec 6. PMID: 17208196. 2. Wang H, Zhao Y, Zhang Z. Age-dependent effects of floxuridine (FUdR) on senescent pathology and mortality in the nematode Caenorhabditis elegans. Biochem Biophys Res Commun. 2019 Feb 12;509(3):694-699. doi: 10.1016/j.bbrc.2018.12.161. Epub 2019 Jan 3. PMID: 30611569.

1: Morihiro K, Ishinabe T, Takatsu M, Osumi H, Osawa T, Okamoto A. Floxuridine Oligomers Activated under Hypoxic Environment. J Am Chem Soc. 2021 Mar 10;143(9):3340-3347. doi: 10.1021/jacs.0c10732. Epub 2021 Mar 1. PMID: 33648338. 2: Medina DJ, Tung PP, Sathya B, Strair RK. Use of floxuridine to modulate the antiviral activity of zidovudine. AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):965-8. doi: 10.1089/aid.1996.12.965. PMID: 8827211. 3: Sato A, Hiramoto A, Kim HS, Wataya Y. Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. Int J Mol Sci. 2020 Aug 16;21(16):5876. doi: 10.3390/ijms21165876. PMID: 32824286; PMCID: PMC7461588. 4: Power DG, Kemeny NE. The role of floxuridine in metastatic liver disease. Mol Cancer Ther. 2009 May;8(5):1015-25. doi: 10.1158/1535-7163.MCT-08-0709. Epub 2009 Apr 21. PMID: 19383854. 5: Aviñó A, Clua A, Bleda MJ, Eritja R, Fàbrega C. Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake. Int J Mol Sci. 2021 May 26;22(11):5678. doi: 10.3390/ijms22115678. PMID: 34073599; PMCID: PMC8199350. 6: Jin C, Zhang H, Zou J, Liu Y, Zhang L, Li F, Wang R, Xuan W, Ye M, Tan W. Floxuridine Homomeric Oligonucleotides "Hitchhike" with Albumin In Situ for Cancer Chemotherapy. Angew Chem Int Ed Engl. 2018 Jul 16;57(29):8994-8997. doi: 10.1002/anie.201804156. Epub 2018 Jun 19. PMID: 29923269; PMCID: PMC6472956. 7: IJzerman NS, Filipe WF, Bruijn P, Buisman FE, Doorn LV, Doornebosch PG, Holster JJ, Grootscholten C, Grünhagen DJ, van Bommel CPE, Homs MYV, Kok NFM, Verhoef C, Koerkamp BG, Kuhlmann KFD, Mathijssen RHJ, Koolen SLW. Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases. Biomed Pharmacother. 2023 Jun;162:114625. doi: 10.1016/j.biopha.2023.114625. Epub 2023 Apr 12. PMID: 37058821. 8: Landowski CP, Song X, Lorenzi PL, Hilfinger JM, Amidon GL. Floxuridine amino acid ester prodrugs: enhancing Caco-2 permeability and resistance to glycosidic bond metabolism. Pharm Res. 2005 Sep;22(9):1510-8. doi: 10.1007/s11095-005-6156-9. Epub 2005 Aug 24. PMID: 16132363. 9: Chirio D, Peira E, Battaglia L, Ferrara B, Barge A, Sapino S, Giordano S, Dianzani C, Gallarate M. Lipophilic Prodrug of Floxuridine Loaded into Solid Lipid Nanoparticles: In Vitro Cytotoxicity Studies on Different Human Cancer Cell Lines. J Nanosci Nanotechnol. 2018 Jan 1;18(1):556-563. doi: 10.1166/jnn.2018.13964. PMID: 29768881. 10: Heidelberger C. Fluorinated pyrimidines. Prog Nucleic Acid Res Mol Biol. 1965;4:1-50. doi: 10.1016/s0079-6603(08)60783-7. PMID: 4226168. 11: Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology. 1989 Feb;9(2):215-8. doi: 10.1002/hep.1840090209. PMID: 2521475. 12: Langman J, Shimada M, Rodier P. Floxuridine and its influence on postnatal cerebellar development. Pediatr Res. 1972 Oct;6(10):758-64. doi: 10.1203/00006450-197210000-00003. PMID: 4265255. 13: Mou Q, Ma Y, Pan G, Xue B, Yan D, Zhang C, Zhu X. DNA Trojan Horses: Self- Assembled Floxuridine-Containing DNA Polyhedra for Cancer Therapy. Angew Chem Int Ed Engl. 2017 Oct 2;56(41):12528-12532. doi: 10.1002/anie.201706301. Epub 2017 Sep 5. PMID: 28806476. 14: Smith JA, Morris A, Duafala ME, Bertino JR, Markman M, Kleinberg M. Stability of floxuridine and leucovorin calcium admixtures for intraperitoneal administration. Am J Hosp Pharm. 1989 May;46(5):985-9. PMID: 2524968. 15: Akhmedov AA, Shurpik DN, Padnya PL, Khadieva AI, Gamirov RR, Panina YV, Gazizova AF, Grishaev DY, Plemenkov VV, Stoikov II. Supramolecular Amphiphiles Based on Pillar[5]arene and Meroterpenoids: Synthesis, Self-Association and Interaction with Floxuridine. Int J Mol Sci. 2021 Jul 26;22(15):7950. doi: 10.3390/ijms22157950. PMID: 34360730; PMCID: PMC8348429. 16: Wang H, Zhao Y, Zhang Z. Age-dependent effects of floxuridine (FUdR) on senescent pathology and mortality in the nematode Caenorhabditis elegans. Biochem Biophys Res Commun. 2019 Feb 12;509(3):694-699. doi: 10.1016/j.bbrc.2018.12.161. Epub 2019 Jan 3. PMID: 30611569. 17: Rivero CW, Britos CN, Lozano ME, Sinisterra JV, Trelles JA. Green biosynthesis of floxuridine by immobilized microorganisms. FEMS Microbiol Lett. 2012 Jun;331(1):31-6. doi: 10.1111/j.1574-6968.2012.02547.x. Epub 2012 Apr 4. PMID: 22428623. 18: Yi JW, Barry NP, Furrer MA, Zava O, Dyson PJ, Therrien B, Kim BH. Delivery of floxuridine derivatives to cancer cells by water-soluble organometallic cages. Bioconjug Chem. 2012 Mar 21;23(3):461-71. doi: 10.1021/bc200472n. Epub 2012 Feb 10. PMID: 22263930. 19: Huczyński A, Antoszczak M, Kleczewska N, Lewandowska M, Maj E, Stefańska J, Wietrzyk J, Janczak J, Celewicz L. Synthesis and biological activity of salinomycin conjugates with floxuridine. Eur J Med Chem. 2015 Mar 26;93:33-41. doi: 10.1016/j.ejmech.2015.01.045. Epub 2015 Jan 27. PMID: 25644674. 20: Lumish M, Thackray J, Do RKG, Caudle KE, Amstutz U, Schwab M, Diasio RB, Jarnagin WR, Cercek A. Precision Management of a Patient With Dihydropyrimidine Dehydrogenase Deficiency and Liver-Predominant Metastatic Rectal Cancer Using Hepatic Arterial Floxuridine. JCO Precis Oncol. 2023 Feb;7:e2200442. doi: 10.1200/PO.22.00442. PMID: 36848609; PMCID: PMC10166539.