Furafylline |
رقم الكتالوجGC32855
One-Click Copy Product Info
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Furafylline هو مثبط قوي وانتقائي للسيتوكروم البشري P450IA2 مع IC50 من 0.07 ميكرومتر
Products are for research use only. Not for human use. We do not sell to patients.
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 |
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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. |
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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 | |
| Canonical SMILES | O=C1N(C2=C(N=C(C)N2)C(N1C)=O)CC3=CC=CO3 | ||
| Formula | C12H12N4O3 | M.Wt | 260.25 |
| الذوبان | DMSO : 12.5 mg/mL (48.03 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8425 mL | 19.2123 mL | 38.4246 mL |
| 5 mM | 768.5 μL | 3.8425 mL | 7.6849 mL |
| 10 mM | 384.2 μL | 1.9212 mL | 3.8425 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)