Fluoroorotic Acid, Ultra Pure
(Synonyms: 5-氟乳清酸) 目录号 : GC11297
Fluoroorotic Acid, Ultra Pure是thymidylate synthase的抑制剂，可以作为酵母分子遗传学中的一种选择剂。
Cas No.:703-95-7
Sample solution is provided at 25 µL, 10mM.
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Fluoroorotic Acid, Ultra Pure is an inhibitor of thymidylate synthase and can be used as a selector in yeast molecular genetics [1]. Fluoroorotic Acid has similar antifungal effects to 5-fluorocytosine and a mild antifungal effect on dermatophytes [2]. Fluoroorotic Acid has strong antimalarial activity [3-4].
In vitro, Fluoroorotic Acid (1nM-100μM; 48h) has dose-dependent and effective antimalarial activity against Plasmodium falciparum, with an IC50 of 6nM. Compared to the vulnerability of the malaria parasites, Fluoroorotic Acid (1nM-100μM; 48h) shows lower cytotoxicity in mammalian cells HT-1080 with an IC50 of 10μM [5].
In vivo, Fluoroorotic Acid (0.2-5mg/kg; ip; every 4 hours for 3 days) can significantly inhibit the parasitemia of the P. yoelii mouse model infected with malaria parasites. Without uridine (dose of 5mg/kg), high-dose treatment of Fluoroorotic Acid shows toxicity to mice [6]. 5-Fluoroorotic acid (2.5, 5.0, and 10mg/kg/day for 3 days; p.o.) used alone can dose-dependently inhibit the number of parasites and parasitemia in mice infected with Plasmodium berghei, with inhibition rates ranging from 92% to 100%. At the highest dose, the combination of Fluoroorotic acid-pyrimethamine and Fluoroorotic acid-dapsone-artesunate has a synergistic effect, with a cure rate of 100% [7].
References:
[1] Boeke JD, Trueheart J, Natsoulis G, Fink GR. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164-175.
[2] Nikolova K, Maneva L, Karamanov G, Golovinsky E. Studies on the antimycotic activity of 5-fluoroorotic acid. Methods Find Exp Clin Pharmacol. 1987;9(2):85-89.
[3] Santiago T C. Understanding phospholipid biosynthesis in the human malaria parasite Plasmodium falciparum using Saccharomyces cerevisiae as a surrogate system[M]. University of Connecticut, 2005.
[4] Biagini G A, Viriyavejakul P, O'neill P M, et al. Functional characterization and target validation of alternative complex I of Plasmodium falciparum mitochondria[J]. Antimicrobial agents and chemotherapy, 2006, 50(5): 1841-1851.
[5] Rathod PK, Khatri A, Hubbert T, Milhous WK. Selective activity of 5-fluoroorotic acid against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 1989;33(7):1090-1094.
[6] Gómez ZM, Rathod PK. Antimalarial activity of a combination of 5-fluoroorotate and uridine in mice. Antimicrob Agents Chemother. 1990;34(7):1371-1375.
[7] Muregi FW, Kano S, Kino H, Ishih A. Plasmodium berghei: efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model. Exp Parasitol. 2009;121(4):376-380.
Fluoroorotic Acid, Ultra Pure是thymidylate synthase的抑制剂，可以作为酵母分子遗传学中的一种选择剂 [1]。Fluoroorotic Acid具有与5-fluorocytosine相近的抗念珠菌的作用，以及温和的抗皮肤癣菌作用 [2]。Fluoroorotic Acid具有较强的抗疟活性 [3-4]。
在体外，Fluoroorotic Acid（1nM-100μM; 48h)对Plasmodium falciparum具有剂量依赖性的有效的抗疟活性，IC50为6nM。相对于疟疾寄生虫的脆弱性，Fluoroorotic Acid（1nM-100μM; 48h)在哺乳动物细胞HT-1080中表现出较低的细胞毒性，IC50为10μM [5]。
在体内，Fluoroorotic Acid（0.2-5mg/kg/d; i.p.; every 4 hours for 3 days）可显著抑制感染P. yoelii小鼠模型中的疟原虫血症。在没有尿苷（剂量为5mg/kg）的情况下，Fluoroorotic Acid高剂量治疗对小鼠表现出毒性 [6]。Fluoroorotic Acid（2.5, 5.0, and 10mg/kg/d for 3 days; p.o.）单独使用能够以剂量依赖性抑制感染Plasmodium berghei后小鼠的寄生虫数量和寄生虫血症，抑制率在92%至100%之间。在最高使用剂量下，Fluoroorotic Acid-pyrimethamine和Fluoroorotic Acid-dapsone-artesunate组合具有协同作用，治愈率为100% [7]。
| Cell experiment [1]: | |
Cell lines | Plasmodium falciparum |
Preparation Method | The following procedure was used for routine assay of antimalarial activity. Various concentrations of Fluoroorotic Acid, dispensed in 25μl of culture medium, were added to individual wells of a 96-well micro-dilution plate. Erythrocytes with 0.25 to 0.5% parasitemia were added to each well in 200μl of culture medium to give a final hematocrit of 1.5%. The plates were incubated at 37°C for 48h under a 5% CO2 atmosphere. Finally, the uptake of 0.5μCi of [G-3H] hypoxanthine (1Ci/mmol) in each well was examined. |
Reaction Conditions | 1nM-100μM; 48h |
Applications | Fluoroorotic Acid exhibits dose-dependent and effective antimalarial activity against Plasmodium falciparum, with an IC50 value of 6nM. |
| Animal experiment [2]: | |
Animal models | ICR mice |
Preparation Method | Plasmodium berghei was intraperitoneally (ip) inoculated into male hybrid ICR mice. Infected mice were orally administered Fluoroorotic Acid starting from the 4th day after infection, at doses of 2.5, 5.0, and 10mg/kg/day, for 3 consecutive days. In some dual or triple experiments, 2.5 and 5.0mg/kg/day of Fluoroorotic Acid were combined with a fixed dose of 1.25 or 2.5mg/kg/day of pyrimethamine (PYR), 1.0 or 2.0mg/kg/day of dapsone (DAP), and 1.0 or 2.0mg/kg/day of artesunate (ART); the doses were four times the corresponding Fluoroorotic Acid doses. All drugs were administered orally, in divided but sequential doses twice daily starting from the 4th day, for three consecutive days, without supplementing with uridine during this period. The efficacy of the drugs was measured by the percentage of parasite reduction observed under a microscope when examining Giemsa-stained thin blood smears collected from the mouse tail vein on the 7th day (starting from the 4th day after infection). |
Dosage form | 2.5, 5.0, and 10mg/kg/day for 3 days; p.o. |
Applications | When Fluoroorotic Acid is used alone, it can dose-dependently inhibit the parasite count and parasitemia in mice infected with Plasmodium berghei, with an inhibition rate ranging from 92% to 100%. At the highest dose used, the combination of Fluoroorotic Acid-PYR and Fluoroorotic Acid-DAP-ART shows a synergistic effect, with a cure rate of 100%. |
References: | |
| Cas No. | 703-95-7 | SDF | |
| 别名 | 5-氟乳清酸 | ||
| 化学名 | 5-fluoro-2,4-dioxo-1H-pyrimidine-6-carboxylic acid | ||
| Canonical SMILES | C1(=C(NC(=O)NC1=O)C(=O)O)F | ||
| 分子式 | C5H3FN2O4 | 分子量 | 174.09 |
| 溶解度 | DMSO:35 mg/mL (201.05 mM) | 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 | 5.7442 mL | 28.7208 mL | 57.4416 mL |
| 5 mM | 1.1488 mL | 5.7442 mL | 11.4883 mL |
| 10 mM | 0.5744 mL | 2.8721 mL | 5.7442 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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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2.
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Quality Control & SDS
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- Purity: >99.00%
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