| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| 5g |
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| Other Sizes |
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Purity: ≥98%
| Targets |
TS/thymidine synthase
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|---|---|
| ln Vitro |
By considerably reducing VEGF expression, doxifluridine (1–10 μM) prevents angiogenesis in FU-MMT-1 cells [1]. At low doses (1 μM), doxifluridine (1-100 μM) slightly increases TSP-1 expression in FU-MMT-1 cells, while at high doses (100 μM), it inhibits TSP-1 expression [1]. In HUVEC cells, dosifluridine (100 μM) can prevent cell division [1].
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| ln Vivo |
In BALB cA Jcl-nu mice, doxifluridine (61.55 mg/kg; gavage; single dose) exhibits anti-cancer action. When combined with TNP-470, this anti-cancer activity can be markedly amplified [1]. Ductal acid synthase activity in the DMH-induced ductal carcinoma center can be inhibited at a dose of 200 mg/kg administered intraperitoneally as a single injection [2].
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| Enzyme Assay |
In vitro tube formation assay.[1]
Tube formation was determined in triplicate in 24-well dishes using an angiogenesis kit according to the manufacturer’s instructions, with a minor modification. FU-MMT-1 cells (1 × 105 cells/well) were co-cultured with human umbilical vein endothelial cells (HUVEC) and fibroblasts, as an in vitro model of tumor angiogenesis, in the presence or absence of the indicated drugs. Doxifluridine, tegafur, 5-FU or TNP-470 was used in this assay.[1] Enzyme immunoassay for VEGF.[1] The concentrations of VEGF in the culture media were determined as previously described using a specific enzyme immunoassay. The medium was obtained on day 9 for each culture. All experiments were repeated independently three times with at least two samples for each treatment. |
| Cell Assay |
Human TSP-1 gene expression in FU-MMT-1 cells and HUVEC.[1]
Low-dose doxifluridine (1 μM) slightly increased TSP-1 expression (P = 0.272) in HUVEC, whereas high-dose doxifluridine (100 μM) reduced TSP-1 expression. Low-dose doxifluridine (1 and 10 μM) significantly increased TSP-1 expression in FU-MMT-1 cells compared with the control group (1 μM, P = 0.041; 10 μM, P = 0.0089).[1] Cytotoxicity assay in HUVEC.[1] Doxifluridine (100 μM) reduced the proliferation of HUVEC compared with the control group, although this did not reach statistical significance (P = 0.079). Meanwhile, TNP-470 (10 and 100 μM) significantly inhibited the proliferation of HUVEC compared with the control group (10 μM, P = 0.041; 100 μM, P = 0.011). However, lower concentrations of doxifluridine (10 μM) were not cytotoxic against HUVEC. |
| Animal Protocol |
In vivo treatments.[1]
The mice were injected subcutaneously with 2 × 105 FU-MMT-1 cells in 0.2 mL of vehicle. Mice that developed tumors measuring 5–10 mm in diameter by day 7 were randomly separated into five groups (n = 5–6/group) and were treated as follows: (i) doxifluridine alone at the MTD of 184.65 mg/kg (the MTD was calculated by referring to the initial in vivo study of doxifluridine, which was administered by gavage); (ii) metronomic doxifluridine at a dose of 61.55 mg/kg; (iii) TNP-470 alone; (iv) metronomic doxifluridine in combination with TNP-470; and (v) control (untreated). Treatments were continued for 8 weeks. Doxifluridine was administered by gavage once daily for 5 consecutive days/week with no prolonged breaks. TNP-470 was injected subcutaneously at a dose of 30 mg/kg three times per week. Tumor growth was monitored by measuring the size of the tumor twice/week, and was calculated as V = length × width2/2. Bodyweight of the mice was measured weekly. |
| References |
[1]. Naganuma Y, et al. Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts. Cancer Sci. 2011 Aug;102(8):1545-52.
[2]. Berne M, et al. Inhibition of thymidylate synthase after administration of doxifluridine in a transplantable colon carcinoma in the rat. Cancer Invest. 1988;6(4):377-83. [3]. Di Bartolomeo M, et al. Integrated treatment with doxifluridine and radiotherapy in recurrent or primary unresectable rectal cancer. A feasibility study. Tumori. 1999 May-Jun;85(3):211-3. |
| Molecular Formula |
C9H11FN2O5
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|---|---|
| Molecular Weight |
246.19
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| Exact Mass |
246.0652
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| Elemental Analysis |
C, 43.91; H, 4.50; F, 7.72; N, 11.38; O, 32.49
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| CAS # |
3094-09-5
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| Related CAS # |
Doxifluridine-d2;84258-25-3
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| Appearance |
White to off-white solid
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| LogP |
-0.96
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| tPSA |
104.55
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| SMILES |
C[C@@H]1[C@H]([C@H]([C@H](N2C(NC(C(F)=C2)=O)=O)O1)O)O
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| InChi Key |
ZWAOHEXOSAUJHY-ZIYNGMLESA-N
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| InChi Code |
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
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| Chemical Name |
1-((2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoropyrimidine-2,4(1H,3H)-dione
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| Synonyms |
Flutron; Furtulon; doxifluridine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~406.19 mM)
DMF : 100 mg/mL (~406.19 mM) H2O : ~20 mg/mL (~81.24 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 27.5 mg/mL (111.70 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0619 mL | 20.3095 mL | 40.6190 mL | |
| 5 mM | 0.8124 mL | 4.0619 mL | 8.1238 mL | |
| 10 mM | 0.4062 mL | 2.0310 mL | 4.0619 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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