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| Targets |
Kobusin has a mixed mechanism of action, targeting two different types of chloride channels. It is an activator of the cystic fibrosis transmembrane conductance regulator (CFTR) and CaCCgie chloride channels, which are important for epithelial fluid transport.. In a contrasting manner, it also functions as an inhibitor (blocker/antagonist) of the ANO1/CaCC (calcium-activated chloride channel) channel.. This unique dual activity makes it a valuable tool for dissecting the roles of various chloride channels in cell physiology.
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| ln Vitro |
Kobusin has the ability to activate the chloride channels of CFTR and CaCCgie (CaCC expressed in gastrointestinal epithelial cells). Interestingly, Kobusin could block ANO1/CaCC chloride channel activity in FRT cells that express ANO1/CaCC[1].
In vitro, Kobusin has been shown to possess the ability to activate the chloride channels CFTR and CaCCgie. Interestingly, while it activates CFTR, it can simultaneously block the activity of ANO1/CaCC chloride channels in FRT (Fischer rat thyroid) cells that express ANO1/CaCC.. This dual activity profile allows researchers to study the opposing functions of CFTR and ANO1 within the same cellular system. |
| ln Vivo |
Kobusin somewhat decreased the gastrointestinal motility of mice in a research on charcoal transit[1].
In vivo, Kobusin has been observed to decrease the gastrointestinal motility of mice in a research model measuring charcoal transit.. This effect is likely related to its ability to block ANO1/CaCC channels, which play a critical role in smooth muscle contraction in the gut. This data suggests that Kobusin can modulate gastrointestinal function in a living organism, highlighting its potential as a tool for studying intestinal physiology and disease. |
| Enzyme Assay |
A cell-free binding or enzyme activity assay for Kobusin would depend on the channel being studied. For its role as an ANO1 inhibitor, a fluorescent thallium (Tl+) influx assay can be performed using membrane vesicles prepared from cells overexpressing ANO1. The assay buffer contains the Tl+ dye, and the increase in fluorescence is measured in real-time as Tl+ enters the vesicles. For CFTR, an ATPase activity assay can be performed using purified CFTR protein reconstituted into liposomes. The activity is measured by quantifying the amount of inorganic phosphate released from ATP hydrolysis in the presence or absence of Kobusin.
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| Cell Assay |
The in vitro cellular assay for Kobusin often involves Fisher rat thyroid (FRT) cells that have been stably transfected to express either CFTR or ANO1/CaCC. Cells are seeded in 96-well black-walled plates with a clear bottom. After reaching confluence, the medium is replaced with a halide-sensitive yellow fluorescent protein (HS-YFP) assay buffer. The cells are then treated with Kobusin for 5-10 minutes. The fluorescence signal is recorded for 2 seconds to establish a baseline, followed by rapid addition of an iodide (I-) solution to quench the fluorescence. The rate of fluorescence decay, which is proportional to CFTR or ANO1 channel activity, is measured, and the IC50 (for ANO1) or EC50 (for CFTR) is calculated..
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| Animal Protocol |
A standard in vivo protocol for Kobusin is based on the charcoal transit model to study gastrointestinal motility. Male ICR mice (25-30 g) are fasted for 18-24 hours. On the day of the experiment, Kobusin is dissolved in a suitable vehicle (e.g., 5% DMSO/95% saline) and administered via intraperitoneal injection at doses ranging from 10-50 mg/kg. After 30 minutes, the mice are given an oral gavage of a 5% charcoal suspension in 10% gum arabic. Thirty minutes later, the mice are euthanized, and the small intestine is removed. The distance traveled by the charcoal meal is measured and expressed as a percentage of the total length of the small intestine. A reduction in the distance traveled indicates a decrease in gastrointestinal motility due to the blockage of ANO1 channels..
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| ADME/Pharmacokinetics |
As a natural product, detailed pharmacokinetic data for Kobusin is limited. Its molecular weight is 370.40 g/mol.. It is a lipophilic compound (LogP = 3.5) and is expected to have good membrane permeability. It is likely metabolized by cytochrome P450 enzymes in the liver. For in vivo research purposes, it is typically dissolved in DMSO and then diluted in saline or a co-solvent mixture for intraperitoneal injection. Its oral bioavailability is likely low due to potential first-pass metabolism, so intraperitoneal administration is often preferred for in vivo studies.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Kobusin is not available. As a natural product extract, acute toxicity is typically low. Standard safety assessments would include an in vitro MTT assay on primary cell lines (e.g., human lung epithelial cells or fibroblasts) to determine its cytotoxicity (IC50). A separate assay would be performed on hERG (human ether-à-go-go-related gene) channels to assess the risk of QT prolongation and cardiotoxicity. No specific genotoxicity or carcinogenicity data is available.
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| References | |
| Additional Infomation |
Demethoxyaschantin, a furan compound, has the chemical name tetrahydro-1H,3H-furano[3,4-c]furan-1-yl]-1,3-benzodioxane, with an additional 3,4-dimethoxyphenyl substituent at the 4-position. It is a plant metabolite. It is a furan compound, lignan, dimethoxybenzene compound, and a member of the benzodioxane group. Kobusin has been reported in Raulinoa echinata, Pandanus odoratissimus, and other organisms with relevant data.
Kobusin is a research-grade natural product and is not approved for clinical use. Its unique pharmacological profile as both a CFTR/CaCCgie activator and an ANO1/CaCC inhibitor makes it a powerful tool for studying chloride channel function. It is particularly useful for investigating the interplay between CFTR and ANO1 in diseases such as cystic fibrosis (where CFTR is deficient) and gastrointestinal disorders (where ANO1 mediates smooth muscle contraction). It is for research use only. |
| Molecular Formula |
C21H22O6
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| Molecular Weight |
370.40
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| Exact Mass |
370.142
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| CAS # |
36150-23-9
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| PubChem CID |
182278
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| Appearance |
White to off-white solid powder
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| LogP |
3.507
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
515
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| Defined Atom Stereocenter Count |
4
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| SMILES |
COC1=C(C=C(C=C1)[C@@H]2[C@H]3CO[C@@H]([C@H]3CO2)C4=CC5=C(C=C4)OCO5)OC
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| InChi Key |
AWOGQCSIVCQXBT-VUEDXXQZSA-N
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| InChi Code |
InChI=1S/C21H22O6/c1-22-16-5-3-12(7-18(16)23-2)20-14-9-25-21(15(14)10-24-20)13-4-6-17-19(8-13)27-11-26-17/h3-8,14-15,20-21H,9-11H2,1-2H3/t14-,15-,20+,21+/m0/s1
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| Chemical Name |
5-[(3S,3aR,6S,6aR)-6-(3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-1,3-benzodioxole
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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 |
| 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: 100 mg/mL (269.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6998 mL | 13.4989 mL | 26.9978 mL | |
| 5 mM | 0.5400 mL | 2.6998 mL | 5.3996 mL | |
| 10 mM | 0.2700 mL | 1.3499 mL | 2.6998 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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