| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
The primary target of Linderane is cytochrome P450 2C9 (CYP2C9), a major drug-metabolizing enzyme responsible for the oxidative metabolism of approximately 15% of clinically used drugs. Linderane acts as an irreversible inhibitor of CYP2C9, meaning it inactivates the enzyme through a mechanism-based process that involves covalent modification of the enzyme active site. The compound inhibits CYP2C9 with a Ki of 1.26 μM. As a mechanism-based inactivator, Linderane requires metabolic activation by CYP2C9 itself to form a reactive intermediate that covalently binds to and irreversibly inhibits the enzyme.
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| ln Vitro |
In vitro, Linderane is a mechanism-based inactivator of CYP2C9 with a Ki of 1.26 μM, indicating potent enzyme inhibition. As an irreversible inhibitor, it demonstrates time- and concentration-dependent inactivation of CYP2C9 activity. The compound's furan-containing sesquiterpenoid structure is believed to be responsible for its mechanism-based inactivation, as furan moieties can be metabolically activated to reactive intermediates that covalently modify cytochrome P450 enzymes.
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| ln Vivo |
In vivo, Linderane relieves pain and spasms. As a mechanism-based inactivator of CYP2C9, it would be expected to cause irreversible inhibition of CYP2C9 in vivo, potentially leading to drug-drug interactions when co-administered with CYP2C9 substrates. The compound's effects on CYP2C9 activity in vivo would depend on the dose and duration of exposure. However, specific in vivo pharmacokinetic or pharmacodynamic data is not detailed in the provided sources.
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| Enzyme Assay |
For CYP2C9 mechanism-based inactivators, standard cell-free assays involve incubation of the test compound with recombinant CYP2C9 enzyme and NADPH (to support metabolic activation) for various time points. Residual enzyme activity is then measured using a specific CYP2C9 substrate (e.g., diclofenac, tolbutamide, or warfarin) and the formation of metabolites is quantified by HPLC or LC-MS. The inactivation kinetics (kinact and Ki) are determined from the time- and concentration-dependent loss of enzyme activity.
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| Cell Assay |
For CYP2C9 inhibitors, standard cellular assays use human hepatocytes or cell lines expressing CYP2C9 (e.g., HepG2 cells transfected with CYP2C9). Cells are treated with the test compound, and CYP2C9 activity is measured by the metabolism of a probe substrate (e.g., diclofenac to 4'-hydroxydiclofenac) quantified by LC-MS. Mechanism-based inactivation can be assessed by pre-incubating cells with the compound and NADPH, followed by washing and measurement of residual enzyme activity.
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| Animal Protocol |
For in vivo evaluation of CYP2C9 inhibitors, standard animal models include pharmacokinetic studies in rodents or dogs where the compound is co-administered with a CYP2C9 probe substrate (e.g., warfarin or tolbutamide). The effect of the test compound on the pharmacokinetics of the probe substrate (e.g., changes in AUC, half-life, clearance) is measured to assess CYP2C9 inhibition in vivo. For Linderane, traditional use as a pain reliever suggests potential analgesic effects in animal models.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for Linderane is not provided in the available sources. The compound has a molecular weight of 260.29 and formula C₁₅H₁₆O₄. As a small, lipophilic sesquiterpenoid, it would be expected to have good oral absorption and tissue distribution. The compound should be stored at 4°C, protected from light. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for Linderane is not provided in the available sources. As a mechanism-based inactivator of CYP2C9, Linderane has the potential to cause drug-drug interactions by irreversibly inhibiting the metabolism of CYP2C9 substrates. This could lead to increased exposure and toxicity of co-administered drugs metabolized by CYP2C9. The compound's safety profile in traditional use suggests some level of tolerability, but comprehensive toxicological evaluation would be required for therapeutic development.
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| References | |
| Additional Infomation |
Linderane is a dioxane compound. It has been reported that Linderane has been found in Dianthus chinensis, Magnolia dentatum, and other organisms in which data are available.
Linderane is a sesquiterpene found in Lindera aggregata that inhibits the cytochrome P450 isoform CYP2C9 with a Ki of 1.26 μM in an irreversible manner. It has the molecular formula C₁₅H₁₆O₄ and molecular weight 260.29. The compound is also known by the IUPAC name 2H-10,1a-(Epoxymethano)oxireno[4,5]cyclodeca[1,2-b]furan-12-one. Linderane relieves pain and spasms. No regulatory approval has been identified. |
| Molecular Formula |
C15H16O4
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|---|---|
| Molecular Weight |
260.2851
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| Exact Mass |
260.104
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| CAS # |
13476-25-0
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| PubChem CID |
6915739
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
434.5±45.0 °C at 760 mmHg
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| Melting Point |
190-191ºC
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| Flash Point |
216.6±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.589
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| LogP |
2.49
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
19
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| Complexity |
457
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C/C/1=C\CC[C@@]23[C@@H](O2)[C@H](C4=C(C1)OC=C4C)OC3=O
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| InChi Key |
KBMSVODXFLAQNJ-DXGHHDSJSA-N
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| InChi Code |
InChI=1S/C15H16O4/c1-8-4-3-5-15-13(19-15)12(18-14(15)16)11-9(2)7-17-10(11)6-8/h4,7,12-13H,3,5-6H2,1-2H3/b8-4+/t12-,13-,15-/m0/s1
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| Chemical Name |
(1S,4E,12S,13S)-5,10-dimethyl-8,14,16-trioxatetracyclo[10.2.2.01,13.07,11]hexadeca-4,7(11),9-trien-15-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 : ~100 mg/mL (~384.19 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8419 mL | 19.2093 mL | 38.4187 mL | |
| 5 mM | 0.7684 mL | 3.8419 mL | 7.6837 mL | |
| 10 mM | 0.3842 mL | 1.9209 mL | 3.8419 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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