Furafylline
(Synonyms: 呋拉茶碱) 目录号 : GC32855
Furafylline，作为治疗哮喘的长效茶碱替代品，是甲基黄嘌呤衍生物。
Cas No.:80288-49-9
Sample solution is provided at 25 µL, 10mM.
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Furafylline, as a long-acting replacement for theophylline in the treatment of asthma, is a methylxanthine derivative[1].
In vitro efficacy test it shown that Furafylline was a potent, non-competitive inhibitor of high affinity phenacetin O-deethylase activity of microsomal fractions of human liver, a reaction catalysed by P450IA2, with an IC50 value of 0.07 µM[1]. In vitro, prior to the initiation of the reaction by the addition of substrate, preincubating microsomes with 10 µM furafylline for 10 min in the presence of NADPH, resulted in marked inhibition of 1A2 activity[2]. In vitro, furafylline has inhibition agaisnt NCMN-O-dealkylation in cynomolgus monkey liver microsomes (CyLM), beagle dog liver microsomes (DLM), minipig liver microsomes (PLM), mouse liver microsomes (MLM) and rat liver microsomes (RLM) with IC50 of 56.36 µM, 26.77 µM, 14.61 µM, 5.73 µM and 1.98 µM, respectively[3].
In vivo test it demonstrated that humanized-liver mice were treated with furafylline (daily oral doses of 13 mg/kg for 3 days) decreased the mean values of the areas under the plasma concentration versus time curves and the maximum concentrations for o-hydroxyphenylacetic acid[4]. In vivo efficacy test it exhibited that beagle dogs were administrated 0.5 and 10 mg/kg orally observed an elimination half-life 2-10 times longer than that of theophylline in a dose-dependent kinetically[5].
References:
Sesardic D, et al. Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man. Br J Clin Pharmacol. 1990 Jun;29(6):651-63.
Clarke SE, et al. Characterization of the inhibition of P4501A2 by furafylline. Xenobiotica. 1994 Jun;24(6):517-26.
Dai Z, et al. Interspecies Variation in NCMN-O-Demethylation in Liver Microsomes from Various Species. Molecules. 2019 Jul 30;24(15):2765.
Miura T, et al. Roles of human cytochrome P450 1A2 in coumarin 3,4-epoxidation mediated by untreated hepatocytes and by those metabolically inactivated with furafylline in previously transplanted chimeric mice. J Toxicol Sci. 2021;46(11):525-530.
Segura J, et al. Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine. J Pharm Pharmacol. 1986 Aug;38(8):615-8.
| Cell experiment [1]: | |
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Cell lines |
human hepatocytes |
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Preparation Method |
25 µM; for 2.2 h at 37 °C |
|
Reaction Conditions |
Sunitinib (10 µM) was incubated with cryopreserved CYP3A5-genotyped human hepatocytes (0.5 × 106 cells/mL in KHB) from 12 individual donors in suspension for 2.2 h at 37 °C. For each donor, incubations were conducted in at least triplicate (three wells per condition). To examine the effect of P450 1A2 inhibitor furafylline (25 µM) on metabolite formation, hepatocytes were coincubated with sunitinib and furafylline in replicates of 2-4 wells per donor, except for donor ZUJ. |
|
Applications |
Furafylline reduced M3 (defluorosunitinib) and M5 (glutathione conjugate) formation by 73.2% ± 0.89% and 81.4% ± 4.84%, respectively, compared to the control. Furafylline reduced M1 (N-desethylsunitinib) formation by only 19.4% ± 5.10% . |
| Animal experiment [2]: | |
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Animal models |
rats |
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Preparation Method |
10 mg/kg; p.o. |
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Dosage form |
Rats were treated 10 mg/kg furafylline orally and test plasma levels of caffeine. |
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Applications |
Plasma levels of caffeine are increased more than 400% in rats given furafylline (10 mg kg-1 p.o.) and caffeine (25 mg kg-1 p.o.) as compared to rats given caffeine alone. |
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References: Burnham EA, et al. Interindividual Variability in Cytochrome P450 3A and 1A Activity Influences Sunitinib Metabolism and Bioactivation. Chem Res Toxicol. 2022 May 16;35(5):792-806. | |
| Cas No. | 80288-49-9 | SDF | |
| 别名 | 呋拉茶碱 | ||
| Canonical SMILES | O=C1N(C2=C(N=C(C)N2)C(N1C)=O)CC3=CC=CO3 | ||
| 分子式 | C12H12N4O3 | 分子量 | 260.25 |
| 溶解度 | DMSO : 12.5 mg/mL (48.03 mM);Water : < 0.1 mg/mL (insoluble) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8425 mL | 19.2123 mL | 38.4246 mL |
| 5 mM | 0.7685 mL | 3.8425 mL | 7.6849 mL |
| 10 mM | 0.3842 mL | 1.9212 mL | 3.8425 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 | ||||||||||
| 计算重置 | ||||||||||
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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet