Flumequine (R-802)

Alias: R-802; R 802; R802; Flumequine
Cat No.:V1413 Purity: ≥98%
Flumequine(formerly R-802;R 802;R802) is a synthetic quinolone, 1st generation and broad-spectrum chemotherapeutic antibiotic that was once used to treat bacterial infections but has beenremoved from market.
Flumequine (R-802) Chemical Structure CAS No.: 42835-25-6
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Flumequine (formerly R-802; R 802; R802) is a synthetic quinolone, 1st generation and broad-spectrum chemotherapeutic antibiotic that was once used to treat bacterial infections but has been removed from market. It functions by 15 μM inhibiting topoisomerase II. Both bacterial gyrase and eukaryotic topoisomerase II, which catalyzes the double-strand DNA breakage reaction, are inhibited by flumequine. The inhibitory effects of FL on topoisomerase II are greater than the influence on bacterial gyrase. Twelve clinical isolates of A. salmonicida have minimum inhibitory concentrations (MICs) for memequine ranging from 0.06 μg/mL to 32 μg/mL.

Biological Activity I Assay Protocols (From Reference)
Targets
Topoisomerase II ( IC50 = 15 μM ); Quinolone
ln Vitro

In vitro activity: Flumequine inhibits both bacterial gyrase and eukaryotic topoisomerase II, the latter of which is in charge of the double-strand DNA breakage reaction. The inhibitory effects of FL on topoisomerase II are greater than the influence on bacterial gyrase. [1] The minimum inhibitory concentration (MIC) of flumequine in 12 clinical isolates of A. salmonicida ranges from 0.06 μg/mL to 32 μg/mL. For the most resistant isolates, methamphetamine exhibits high E(max) values of 16, indicating a significant contribution of efflux to the resistance phenotype. The association between high E(max) values and a significantly lower level of accumulation is confirmed by flumequine accumulation experiments. [2]

ln Vivo
Flumequine (4000 ppm, oral diet) causes dose-dependent DNA damage in adult mice's stomach, colon, and bladder three hours after administration, but not twenty-four hours later.[1] Flumequine has a 44.7% bioavailability rate in Atlantic salmon after medicated feed is given orally. After being administered intravenously to Atlantic salmon, memequine causes distribution volumes at steady state of 3.5 L/kg, elimination half-life (t 1/2) of 22.8 hours, and area under plasma drug concentration-time curve (AUC) of 140 μg×hours/mL.[3] For the aquatic weed Lythrum salicaria L., memequine (100 mg/L) decreases the mean number of secondary roots, hypocotyle, cotyledon, and root length.[4] The oral dosage of flumequine (10 mg/kg) causes the steady-state volumes of distribution (Vss) to be 2.41 L/kg for cod and 2.15 L/kg for wrasse after intravenous entry. After administering 10 mg/kg of flumequine orally, the total body clearances (Cl) for cod and wrasse are 0.024 L/h.kg and 0.14 L/h.kg, respectively, and the elimination half-lives (t1/2 λ z) are calculated to be 75 hours. Flumequine administered orally results in oral bioavailabilities (F) of 65% for cod and 41% for wrasse.[5]
Cell Assay
The Chinese hamster lung cell line CHL/IU is routinely cultured in monolayer form at 37°C in a 5% CO2 environment using Dulbecco's modified MEM medium supplemented with 10% fetal bovine serum. For one hour, exponentially growing cells are exposed to a solution of flumequine (R-802) dissolved in DMSO. The dose range is selected to extract both severely damaged and undamaged cells. After being treated with Flumequine (R-802) the cells are embedded in 1% saline-dissolved GP42 agarose. For every dosage, the number and viability of cells are ascertained.
Animal Protocol
Once a week has passed for acclimatization, 4 and 7 week old male ddY infants and young adults are used. At less than 500 mg/kg, groups receive a single oral dose of flumequine (R-802). Eight organs—the stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow—are removed from adult mice following their sacrifice three and twenty-four hours of therapy. Liver removal occurs when young mice are sacrificed three and twenty-four hours after treatment. Flumequine (R-802) genotoxicity in the developing liver of adult mice is investigated in a different study. The left lateral lobe, left medial lobe, and right lateral lobe of the liver are removed from male mice that are 8 weeks old after they are given ether anesthesia for this purpose. Mice are given Flumequine (R-802) orally once every four days following hepatectomy. After 3 hours of FL treatment, they are sacrificed, and samples of their regenerated livers are taken. At every predetermined time, slides for the comet assay are prepared.
References

[1]. Toxicol Sci . 2002 Oct;69(2):317-21.

[2]. J Med Microbiol . 2004 Sep;53(Pt 9):895-901.

[3]. Antimicrob Agents Chemother . 1995 May;39(5):1059-64.

[4]. Chemosphere . 2000 Apr;40(7):741-50.

[5]. J Vet Pharmacol Ther . 2000 Jun;23(3):163-8.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C14H12FNO3
Molecular Weight
261.25
Exact Mass
261.08
Elemental Analysis
C, 64.36; H, 4.63; F, 7.27; N, 5.36; O, 18.37
CAS #
42835-25-6
Related CAS #
42835-25-6
Appearance
Solid powder
SMILES
CC1CCC2=C3N1C=C(C(=O)C3=CC(=C2)F)C(=O)O
InChi Key
DPSPPJIUMHPXMA-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H12FNO3/c1-7-2-3-8-4-9(15)5-10-12(8)16(7)6-11(13(10)17)14(18)19/h4-7H,2-3H2,1H3,(H,18,19)
Chemical Name
7-fluoro-12-methyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid
Synonyms
R-802; R 802; R802; Flumequine
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: 3~7.7 mg/mL (~11.5~29.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.8278 mL 19.1388 mL 38.2775 mL
5 mM 0.7656 mL 3.8278 mL 7.6555 mL
10 mM 0.3828 mL 1.9139 mL 3.8278 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.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Accumulation of flumequine by strains ATCC 14174 (•), 15 (▪), 56 (▵) and 74 (⋄). J Med Microbiol . 2004 Sep;53(Pt 9):895-901.
  • Migration of nuclear DNA from CHL cells treated with flumequine. Toxicol Sci . 2002 Oct;69(2):317-21.
  • Migration of nuclear DNA from the liver of infant mice and regenerating liver of adult mice treated with flumequine. Toxicol Sci . 2002 Oct;69(2):317-21.
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