Floxuridine
(Synonyms: 氟尿苷; 5-Fluorouracil 2'-deoxyriboside) 目录号 : GC18014
Floxuridine是一种抗代谢药物类抗癌药，是胸苷酸合酶的特异性抑制剂。
Cas No.:50-91-9
Sample solution is provided at 25 µL, 10mM.
Floxuridine is an oncology drug classified as an antimetabolite and a specific inhibitor of thymidylate synthase[1]. Thymidylate synthase is the sole enzyme that catalyzes the de novo conversion of dUMP to dTMP, making it indispensable for DNA synthesis[2]. Floxuridine is usually used in antitumor and antiviral research[3].
In vitro, treatment of AsPC-1 pancreatic ductal cancer cells with Floxuridine (0.25–4mM; 2h) concentration-dependently inhibits cell proliferation and suppresses [³H]Gly-Sar uptake[4]. Treatment of OVCAR-8 ovarian cancer cells with Floxuridine (300μM; 24h) inhibits cell proliferation, induces the DNA-damage marker γ-H2AX, activates the ATM/ATR-Chk1/Chk2 checkpoint, and blocks cell G₁/S-phase recovery[5].
In vivo, Floxuridine (2.5mg/kg; single intraperitoneal injection) markedly inhibits multiple regulatory systems including Sae and Agr, induces prophages lysis, attenuates Staphylococcus aureus virulence, and raises the 7-day survival rate of mice from 0% to about 80% without altering blood glucose or blood cell counts in Staphylococcus aureus blood infects mice[6]. Floxuridine (2.5mg/kg; single intraperitoneal injection) significantly increased [¹⁸F]FLT uptake in various human tumor xenografted mouse models, including Ramos lymphoma, MDA-MB231 breast cancer, SKBR3 breast cancer, LS174T colon cancer, and WiDr colon cancer, with an average increase of 3.2–7.8 times[7].
References:
[1] Landowski CP, Vig BS, Song X, Amidon GL. Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs. Mol Cancer Ther. 2005;4(4):659-667.
[2] Ackland SP, Beale P, Peters GJ. Thymidylate synthase inhibitors. Cancer Chemother Biol Response Modif. 2003;21:1-28.
[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;21(16):5876.
[4] 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;5(5):717-727.
[5] Huehls AM, Wagner JM, Huntoon CJ, et al. Poly(ADP-Ribose) polymerase inhibition synergizes with 5-fluorodeoxyuridine but not 5-fluorouracil in ovarian cancer cells. Cancer Res. 2011;71(14):4944-4954.
[6] Yeo WS, Arya R, Kim KK, Jeong H, Cho KH, Bae T. The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus. Sci Rep. 2018;8(1):2521.
[7] Viertl D, Bischof Delaloye A, Lanz B, et al. Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography. Mol Imaging Biol. 2011;13(2):321-331.
Floxuridine是一种抗代谢药物类抗癌药，是胸苷酸合酶的特异性抑制剂[1]。胸苷酸合酶是催化dUMP转化为dTMP的唯一酶，对DNA合成至关重要[2]。Floxuridine通常用于抗肿瘤和抗病毒研究[3][4]。
在体外，用Floxuridine（0.25–4mM；2小时）处理AsPC-1胰腺导管癌细胞可浓度依赖性地抑制细胞增殖并抑制[³H]Gly-Sar的摄取[5]。用Floxuridine（300μM；24小时）处理OVCAR-8卵巢癌细胞可抑制细胞增殖，诱导DNA损伤标志物γ-H2AX，激活ATM/ATR-Chk1/Chk2检查点，并阻断细胞从G₁/S期阻滞中恢复[2]。
在体内，Floxuridine（2.5mg/kg；单次腹腔注射）显著抑制Sae、Agr等多套毒力调控系统，诱导噬菌体裂解，降低金黄色葡萄球菌毒力，并使血液感染小鼠的7天存活率由0%升至约80%，且未引起血糖或血细胞计数变化[6]。Floxuridine（2.5mg/kg；单次腹腔注射）显著增加了多种人肿瘤异种移植小鼠模型（包括Ramos淋巴瘤、MDA-MB231乳腺癌、SKBR3乳腺癌、LS174T结肠癌和WiDr结肠癌）对[¹⁸F]FLT的摄取，平均增加了3.2–7.8倍[7]。
| Cell experiment [1]: | |
Cell lines | AsPC-1 cells |
Preparation Method | AsPC-1 cells were seeded onto 96-well plates at 125,000 cells per well and allowed to attach/grow for 24h before drug solutions were added. The culture medium (RPMI-1640 + 10% fetal bovine serum) was removed, and the cells were gently washed once with sterile pH 6.0 uptake buffer. Floxuridine was 2-fold serially diluted in pH 6.0 uptake buffer from 4 to 0.25mM. Buffer alone was used as 100% viability control. The wash buffer was removed, and 25µL of drug solution per well was added and incubated at 37°C for 2h with AsPC-1 cells in the cell incubator. After this time period, the drug solutions were removed and the cells were gently washed twice with sterile uptake buffer. Fresh culture medium was then added to each well after washing, and the cells were allowed to recover for 24h before evaluating cell viability Via 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays. A mixture (30µL) containing XTT (1mg/mL) in sterile RPMI-1640 without phenol red and phenazine methosulfate (N-methyl dibenzopyrazine methyl sulfate in sterile PBS, 0.383mg/mL) reagents was added to the cells and incubated at 37°C for 1h, after which the absorbance at 450nm was read. GI50 values were calculated using GraphPad Prism version 3.0 by nonlinear data fitting. |
Reaction Conditions | 0.25–4mM; 2h |
Applications | Floxuridine concentration-dependently inhibits AsPC-1 cells proliferation. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | An overnight culture of S. aureus was 100-fold diluted into fresh TSB and further incubated at 37°C for 4h. Cells were collected by centrifugation, washed with sterile PBS, and suspended in sterile PBS to OD600=4 (1×109CFU/mL). S. aureus USA300 was administered into 10 sex-matched 8-week-old C57BL/6 mice via retro-orbital injection; then, at 1h post-infection, the Floxuridine (2.5mg/kg body weight) was injected into the mice via the intraperitoneal route. The mice were watched for 2 weeks. |
Dosage form | 2.5mg/kg; single intraperitoneal injection |
Applications | Floxuridine markedly raises the 7-day survival rate of mice from 0% to about 80%. |
References: | |
| Cas No. | 50-91-9 | SDF | |
| 别名 | 氟尿苷; 5-Fluorouracil 2'-deoxyriboside | ||
| 化学名 | 5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione | ||
| Canonical SMILES | C1C(C(OC1N2C=C(C(=O)NC2=O)F)CO)O | ||
| 分子式 | C9H11FN2O5 | 分子量 | 246.19 |
| 溶解度 | ≥ 12.3mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0619 mL | 20.3095 mL | 40.619 mL |
| 5 mM | 0.8124 mL | 4.0619 mL | 8.1238 mL |
| 10 mM | 0.4062 mL | 2.031 mL | 4.0619 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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