| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| ln Vitro |
Isosinensetin significantly inhibited P-glycoprotein (P-gp)-mediated transport of digoxin in MDR1-MDCKII cells, with an inhibition percentage of 76.68% at a tested concentration of 100 μM. Its concentration-dependent inhibition of P-gp was confirmed, yielding an IC50 value of 4.2 μM [2].
Isosinensetin (at a concentration of 8.4 μM, which is two-fold its IC50) increased the cytotoxicity of paraquat (a P-gp substrate) in MDR1-MDCKII cells, indicating that its inhibition of P-gp efflux function leads to increased intracellular accumulation and toxicity of paraquat [2]. Isosinensetin (at a concentration of 8.4 μM, two-fold its IC50) increased the cytotoxicity of taxol in both wild-type MX-1 breast cancer cells and taxol-resistant MX-1/T cells, suggesting its potential to modulate P-gp-mediated drug resistance [2]. A cytotoxicity assay (MTT) showed that Isosinensetin was non-toxic to MDR1-MDCKII cells after 4 hours of exposure at concentrations up to 150 μM [2]. |
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| ln Vivo |
Co-administration of Isosinensetin (25 mg/kg, oral) with digoxin (0.25 mg/kg, oral) in rats significantly increased the systemic exposure of digoxin. The area under the concentration-time curve from zero to the last measurable time point (AUC0-t) of digoxin increased by 81.51%, and the maximum plasma concentration (Cmax) increased by 169.39%. The apparent volume of distribution (Vd/F) and oral clearance (CL/F) of digoxin were decreased [2].
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| Cell Assay |
Cytotoxicity Assay (MTT): MDR1-MDCKII cells were seeded in 96-well plates at a density of 3×10^4 cells per well and cultured for 48 hours. The cells were then incubated with varying concentrations of Isosinensetin (0-150 μM) or control buffer for 4 hours. After incubation, the supernatant was removed, and MTT solution was added to each well followed by another 4-hour incubation. The formazan crystals formed were dissolved, and the absorbance was measured at 490 nm to determine cell viability [2].
P-gp Inhibition Transport Assay: MDR1-MDCKII cell monolayers grown on transwell inserts were used. Cells were washed and pre-incubated with Isosinensetin at varying concentrations (0-150 μM) or control buffer for 30 minutes. The assay was initiated by replacing the medium in either the apical (AP) or basolateral (BL) chamber with digoxin (5 μM) dissolved in buffer containing the corresponding concentration of Isosinensetin. Samples were collected from the receiver chamber at 0.5, 1, 1.5, and 2 hours, with fresh buffer added to maintain constant volume. Digoxin concentration was measured by LC-MS/MS. The apparent permeability coefficients (Papp) and percent inhibition of P-gp-mediated efflux were calculated [2]. Paraquat Cytotoxicity Modulation Assay: MDR1-MDCKII cells were seeded in 96-well plates. Cells were exposed to a range of paraquat concentrations (0-1000 μM) for 24 hours, either alone or in combination with Isosinensetin at a fixed concentration of 8.4 μM (two-fold its IC50). Cell viability was assessed using the MTT method as described above [2]. Taxol Cytotoxicity Modulation Assay: Wild-type MX-1 and taxol-resistant MX-1/T cells were seeded in 96-well plates. Cells were exposed to taxol (75 μM) for 24 hours, either alone or in combination with Isosinensetin at a fixed concentration of 8.4 μM (two-fold its IC50). Cell viability was assessed using the MTS method, where MTS reagent was added to each well after incubation, followed by a further 4-hour incubation before measuring absorbance at 490 nm [2]. |
| Animal Protocol |
In Vivo Pharmacokinetic Interaction Study in Rats: Male Sprague-Dawley rats (190-220 g) were fasted overnight with free access to water before the experiment. Rats were divided into groups (n=5). Isosinensetin was suspended in 0.5% sodium carboxymethylcellulose (CMC-Na) solution and administered orally at a dose of 25 mg/kg. Thirty minutes after Isosinensetin administration, digoxin (0.25 mg/kg) was administered orally. Blood samples (0.2 mL) were collected from the orbital vein at predetermined time points (pre-dose, 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-digoxin dosing). Plasma was separated by centrifugation and stored at -20°C until LC-MS/MS analysis for digoxin concentration [2].
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| ADME/Pharmacokinetics |
Drug interactions (in vivo): In rats, oral administration of isoxin (25 mg/kg) significantly altered the pharmacokinetics of digoxin, increasing the exposure (AUC) and peak concentration (Cmax) of digoxin and decreasing its clearance. This suggests that there may be a risk of pharmacokinetic interactions when isoxin is administered concomitantly with P-gp substrate drugs such as digoxin [2]. In vitro cytotoxicity: Isoxin did not show cytotoxicity to MDR1-MDCKII cells after 4 hours of exposure at concentrations up to 150 μM [2].
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| References |
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| Additional Infomation |
Isosinensetin are ether compounds belonging to the flavonoid class.
Isosinensetin have been reported to be found in citrus (Citrus leiocarpa), aucupifolia (Citrus myrtifolia), and other organisms with relevant data. See also: orange peel (part); sour orange (Citrus aurantium) peel (part). Isosinensetin were identified as one of the polymethoxyflavones (PMFs) found in the peel of green mandarin orange (Pericarpium Citri Reticulatae Viride). It accounted for 0.2% of the stable PMF mixture obtained by the extraction and separation procedure described [1]. Identification of the isoflavone (compound 1) was based on its UV spectra, mass spectrometry data, and elution sequence. No further separation or NMR structural confirmation was performed in this study as described in the cited literature [1]. The literature indicates that PMFs have antimutagenic and antitumor properties and therefore may have chemopreventive potential. However, no specific bioactivity data of Isosinensetin themselves are provided in the reference [1]. Isosinensetin are polymethoxyflavonoids found in citrus fruits such as oranges. Among the 75 flavonoids tested in this study, Isosinensetin were identified as one of the most effective P-gp inhibitors [2]. Molecular docking analysis suggests that the inhibitory effect of Isosinensetin on P-gp may be related to the π-π interaction of amino acid residues such as Phe974 and Val978, rather than the formation of hydrogen bonds [2]. Pharmacophore modeling suggests that the hydrophobic groups on the B ring of flavonoids are crucial for P-gp inhibitory activity. Isosinensetin contain such hydrophobic groups (methoxy substitution) [2]. |
| Molecular Formula |
C20H20O7
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|---|---|
| Molecular Weight |
372.3686
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| Exact Mass |
372.12
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| CAS # |
17290-70-9
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| PubChem CID |
632135
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.244±0.06 g/cm3 (20 ºC 760 Torr)
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| Boiling Point |
565.3±50.0 °C at 760 mmHg
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| Melting Point |
198-199 ºC
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| Flash Point |
248.4±30.2 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.566
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| LogP |
2.88
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
548
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UYCWETIUOAGWIL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H20O7/c1-22-13-7-6-11(8-15(13)23-2)14-9-12(21)18-16(24-3)10-17(25-4)19(26-5)20(18)27-14/h6-10H,1-5H3
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| Chemical Name |
2-(3,4-dimethoxyphenyl)-5,7,8-trimethoxychromen-4-one
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~12.5 mg/mL (~33.57 mM)
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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 : PEG300 ：Tween 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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6855 mL | 13.4275 mL | 26.8550 mL | |
| 5 mM | 0.5371 mL | 2.6855 mL | 5.3710 mL | |
| 10 mM | 0.2686 mL | 1.3428 mL | 2.6855 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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