| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Kadsurenone specifically targets the Platelet-Activating Factor (PAF) receptor (PTAFR), a GPCR. It acts as a PAF receptor antagonist. PAF is a potent pro-inflammatory phospholipid mediator. By blocking this receptor, Kadsurenone disrupts downstream signaling cascades that promote cell migration and osteoclastogenesis. It is an important mediator of endotoxin-induced hypotension in rats, and antagonists can block this effect.
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| ln Vitro |
In vitro, Kadsurenone acts as a specific antagonist of Platelet-Activating Factor. By blocking the PAF/PTAFR signaling pathway, it is used to study the role of PAF in various cellular processes. It inhibits PAF-induced cellular responses, such as platelet aggregation and calcium mobilization. Its activity is based on competitive antagonism of the receptor, preventing the binding of the natural ligand PAF.
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| ln Vivo |
The hepatobiliary system excretes kadsurenone (IV; 20 and 30 mg/kg), yet the P-glycoprotein (P-gp) transport system might not be in charge of this process[1].
In vivo, Kadsurenone shows potential as a treatment for breast cancer bone metastases. Animal studies suggest that PAF/PTAFR signaling is involved in bone metastasis. As a PAF receptor antagonist, Kadsurenone can disrupt this pathway, thereby reducing the development of metastases in the bone microenvironment. It is also known that PAF is an important mediator of endotoxin-induced hypotension in rats, and Kadsurenone can block this effect. |
| Enzyme Assay |
The standard protocol for assessing PAF receptor antagonism uses a radioligand binding assay with [3H]-PAF. Membranes are prepared from rabbit platelets. The membranes are incubated with 1-2 nM [3H]-PAF and increasing concentrations of Kadsurenone (1 nM to 100 uM) in binding buffer (Tris-HCl, pH 7.5, containing 0.25% BSA) for 60 minutes at 4degC. Non-specific binding is determined in the presence of 10 uM unlabeled PAF. Bound and free ligands are separated by filtration through Whatman GF/C filters. The filters are washed and counted using a liquid scintillation counter. Specific binding is calculated, and Ki values are determined.
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| Cell Assay |
For in vitro functional assays, human platelets are isolated from platelet-rich plasma (PRP) via centrifugation. The platelet pellet is washed and resuspended in Tyrode's buffer. Platelets are pre-incubated with Kadsurenone (0.1-10 uM) for 5 minutes. Aggregation is induced by the addition of PAF (100 nM). Platelet aggregation is measured using an aggregometer. The extent of aggregation is measured as the percentage change in light transmission. Kadsurenone should inhibit PAF-induced aggregation in a concentration-dependent manner. Alternatively, calcium mobilization in PAF-stimulated platelets can be measured using a fluorescent calcium indicator (e.g., Fura-2 AM).
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| Animal Protocol |
Animal/Disease Models: SD (Sprague-Dawley) rats[1]
Doses: 0 and 30 mg/kg Route of Administration: IV Experimental Results: Could go through hepatobiliary excretion. An in vivo protocol for Kadsurenone would involve a mouse model of breast cancer bone metastasis. Female BALB/c nude mice are injected with luciferase-labeled MDA-MB-231 human breast cancer cells via the left cardiac ventricle. Mice are then randomized into groups. Kadsurenone is administered intraperitoneally at doses of 1-20 mg/kg daily for 4-6 weeks. Tumor growth and bone metastasis are monitored twice weekly via bioluminescence imaging using an IVIS system. At the end of the study, hind limbs are collected, fixed, and subjected to micro-CT scanning to quantify bone destruction. Osteoclast numbers are quantified by TRAP staining. Kadsurenone should reduce the incidence of bone metastases. |
| ADME/Pharmacokinetics |
Specific PK data for Kadsurenone is not available in standard databases. As a natural product lignan, its properties are typically characterized by low water solubility and moderate metabolic stability. Oral bioavailability is likely low due to extensive first-pass metabolism. For in vivo studies, it is often administered intraperitoneally using formulations containing co-solvents such as DMSO and PEG400 to improve solubility and absorption.
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| Toxicity/Toxicokinetics |
Toxicology data for Kadsurenone is not available. As a natural product, Kadsurenone is generally considered to have a low toxicity profile. However, as a PAF antagonist, its primary pharmacological effect would be inhibition of PAF-induced inflammatory responses. Potential toxicities may include immune system modulation. Standard acute toxicity testing in mice (up to 1000 mg/kg i.p.) would determine the LD50 and maximum tolerated dose. No genotoxicity or carcinogenicity data is available.
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| References | |
| Additional Infomation |
Carsuzoline belongs to the benzofuran class of compounds. It has been reported to exist in Piper hancei, Piper kadsura, and other organisms with relevant data.
Kadsurenone is a research-grade natural product and is not approved for clinical use. Its molecular formula is C21H24O5 with a molecular weight of 356.41. It is isolated from stems of Piper kadsura (Haifenteng). The compound has a molecular weight of 356.41. Kadsurenone is a useful tool for studying the role of PAF signaling in inflammation, cancer metastasis, and endotoxic shock. Its discovery highlights the value of natural products as leads for drug discovery. |
| Molecular Formula |
C21H24O5
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|---|---|
| Molecular Weight |
356.41
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| Exact Mass |
356.162
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| CAS # |
95851-37-9
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| Related CAS # |
(±)-7-epi-Kadsurenone;245648-20-8
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| PubChem CID |
122159
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| Appearance |
White to off-white solid powder
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| LogP |
3.765
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
622
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@@H]1[C@H](OC2=CC(=O)C(=C[C@]12OC)CC=C)C3=CC(=C(C=C3)OC)OC
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| InChi Key |
VDYACOATPFOZIO-UBWHGVKJSA-N
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| InChi Code |
InChI=1S/C21H24O5/c1-6-7-15-12-21(25-5)13(2)20(26-19(21)11-16(15)22)14-8-9-17(23-3)18(10-14)24-4/h6,8-13,20H,1,7H2,2-5H3/t13-,20+,21+/m1/s1
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| Chemical Name |
(2S,3R,3aS)-2-(3,4-dimethoxyphenyl)-3a-methoxy-3-methyl-5-prop-2-enyl-2,3-dihydro-1-benzofuran-6-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.8058 mL | 14.0288 mL | 28.0576 mL | |
| 5 mM | 0.5612 mL | 2.8058 mL | 5.6115 mL | |
| 10 mM | 0.2806 mL | 1.4029 mL | 2.8058 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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