| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Vitamin K-dependent coagulation factors (anticoagulant mechanism); tubulin (microtubule polymerization); mycobacterial enzymes; succinate ubiquinone reductase (mitochondrial complex II).
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| ln Vitro |
Ferulitol interacts with respiratory chain complex II and adenine nucleotide translocase (ANT) to suppress the oxidative phosphorylation pathway. Without affecting mitochondrial respiration, ferulol suppresses adenine nucleotide translocase at low doses, preventing the generation of ATP. Fertulol reduces the need for oxygen at higher quantities. While complex II's succinate dehydrogenase activity remains unchanged, fermulol specifically inhibits succinate ubiquinone reductase [1]. Similar to thienoyltrifluoroacetone (TTFA), fermentol also inhibits the activity of succinate ubiquinone reductase (SQR) in a concentration-dependent way [1].
Ferulenol is a prenylated 4-hydroxycoumarin with multiple in vitro activities. It acts as a potent anticoagulant by inhibiting vitamin K-dependent coagulation factors (factors II, VII, IX, X), with a mechanism similar to warfarin but reportedly higher activity. Ferulenol exhibits antibiotic activity against mycobacteria, including Mycobacterium tuberculosis and other mycobacterial species. As a microtubule-interacting agent, ferulenol stimulates tubulin polymerization in vitro (similar to taxol) and inhibits colchicine binding to tubulin, leading to disruption of the mitotic spindle and cell cycle arrest. It shows taxol-like and dose-dependent cytotoxicity against various human tumor cell lines (e.g., HeLa, MCF-7, others). Ferulenol specifically inhibits succinate ubiquinone reductase (mitochondrial complex II) at the level of the ubiquinone cycle, leading to disruption of mitochondrial membrane potential and induction of mitochondrial dysfunction, which may contribute to its cytotoxic effects. It also exhibits antithrombotic activity by depressing the activity of all vitamin K-dependent coagulation factors. The compound is a potent inhibitor of ATP synthesis in mitochondria. In hepatocytes, ferulenol induces toxicity, which has been reported in both in vitro and in vivo studies. The IC50 for cytotoxicity varies by cell line but is typically in the low micromolar range (1-10 microM). |
| ln Vivo |
Ferulenol has been studied in vivo in various animal models, primarily for its anticoagulant and toxic effects. In rodent models, ferulenol shows more potent anticoagulant activity than warfarin, as measured by prothrombin time (PT) and activated partial thromboplastin time (aPTT) prolongation. In a rat model, oral or intraperitoneal administration of ferulenol at doses of 0.5-2 mg/kg results in significant anticoagulation. However, ferulenol also induces hepatocyte toxicity in vivo, as evidenced by elevated serum liver enzymes (ALT, AST) and histopathological changes in the liver (necrosis, inflammation). The compound causes severe poisoning in grazing animals (e.g., sheep, goats) that ingest Ferula communis, leading to a condition called "ferulosis" characterized by coagulopathy (hemorrhage) and hepatotoxicity. Ferulenol reduces the activity of all vitamin K-dependent coagulation factors, leading to a prohemorrhagic state. It disrupts mitochondrial membrane potential in liver cells, leading to ATP depletion and cell death. The LD50 in rodents has been reported in the range of 5-20 mg/kg (oral) depending on the species. The compound is not used therapeutically due to its narrow therapeutic window and hepatotoxicity.
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| Enzyme Assay |
The anticoagulant activity of ferulenol is measured using a prothrombin time (PT) assay in plasma. Citrated plasma from rats or humans is incubated with varying concentrations of ferulenol (0.1-100 microM, dissolved in DMSO, final DMSO ≤0.1%) for 30 minutes at 37degC. Recombinant human thromboplastin (tissue factor) is added, and the clotting time is measured using a coagulometer. The concentration that doubles the PT is calculated. Alternatively, the activity of specific vitamin K-dependent factors (factors II, VII, IX, X) can be measured using factor-deficient plasma in a one-stage clotting assay. For the microtubule polymerization assay, purified tubulin (1 mg/mL) is incubated in PEM buffer (80 mM PIPES, pH 6.9, 1 mM EGTA, 1 mM MgCl2) containing 1 mM GTP and varying concentrations of ferulenol (0.1-10 microM) at 37degC. Tubulin polymerization is monitored by measuring the increase in absorbance at 350 nm (due to light scattering from microtubules) over 30-60 minutes using a UV-Vis spectrophotometer. Taxol (10 microM) is used as a positive control. For the colchicine binding inhibition assay, tubulin is incubated with [3H]-colchicine (1 microM) and varying concentrations of ferulenol (0.1-100 microM) for 2 hours at 37degC. The mixture is filtered through DEAE-cellulose filters, washed, and the bound radioactivity is measured by scintillation counting. The IC50 is calculated. For mitochondrial complex II inhibition, isolated mitochondria are incubated with ferulenol, and succinate-ubiquinone reductase activity is measured spectrophotometrically by following the reduction of 2,6-dichlorophenolindophenol (DCPIP) at 600 nm.
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| Cell Assay |
The cytotoxic activity of ferulenol is assessed using various cancer cell lines (e.g., HeLa, MCF-7, A549, HepG2) and primary hepatocytes. Cells are seeded in 96-well plates at 5-10×103 cells per well in appropriate culture medium containing 10% FBS. After overnight attachment, the medium is replaced with fresh medium containing varying concentrations of ferulenol (0.01-100 microM, 3-fold serial dilutions, prepared in DMSO, final DMSO ≤0.1%). Control wells receive DMSO alone. Plates are incubated for 24-72 hours at 37degC. Cell viability is measured using an MTT assay (add 10 microL of 5 mg/mL MTT per well, incubate for 4 hours, add 100 microL of solubilization buffer (10% SDS in 0.01 M HCl), incubate overnight, measure absorbance at 570 nm). The IC50 is calculated. To assess mitochondrial membrane potential (deltaΨm), cells are treated with ferulenol (1-10 microM) for 1-4 hours, then stained with a fluorescent dye such as JC-1 or TMRM (tetramethylrhodamine methyl ester). For JC-1, a shift from red (aggregates, high deltaΨm) to green (monomers, low deltaΨm) is quantified by flow cytometry or fluorescence microscopy (excitation 488 nm, emission 530 nm (green) and 590 nm (red)). The ratio of red/green fluorescence is calculated. For ATP levels, cells are treated with ferulenol for 1-4 hours, lysed, and ATP is quantified using a bioluminescent ATP assay kit (e.g., CellTiter-Glo). Ferulenol treatment should cause a rapid decrease in ATP levels. For hepatocyte toxicity, primary mouse or rat hepatocytes are isolated and treated with ferulenol (1-100 microM) for 24 hours; cell viability is measured, and the supernatant is collected for measurement of ALT and AST release (indicating cell membrane damage).
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| Animal Protocol |
In vivo studies of ferulenol are typically performed in rodents to assess its anticoagulant and hepatotoxic effects. For anticoagulant activity, male Wistar rats (200-250 g) are fasted overnight and then administered ferulenol via oral gavage at doses of 0.5, 1, 2, 5 mg/kg suspended in a vehicle (e.g., 0.5% methylcellulose or corn oil). Warfarin (0.5-1 mg/kg) is used as a positive control. Control rats receive vehicle alone. Blood samples (0.5-1 mL) are collected from the retro-orbital plexus or tail vein into sodium citrate tubes at baseline (0 h) and at various time points (4, 8, 12, 24, 48, 72 hours) after administration. Platelet-poor plasma is prepared by centrifugation at 3000 rpm for 10 minutes. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are measured using a coagulometer. The PT is expressed as the International Normalized Ratio (INR). The anticoagulant effect of ferulenol is typically maximal at 12-24 hours and can persist for 48-72 hours. For hepatotoxicity assessment, rats are treated with ferulenol (2-10 mg/kg, oral or i.p.) and euthanized after 24-48 hours. Blood is collected for serum ALT, AST, alkaline phosphatase (ALP), and bilirubin measurements. Livers are excised, weighed, and fixed in 10% formalin for histopathological examination (H&E staining) to assess necrosis, inflammation, and steatosis. For toxicity studies, the LD50 is determined by administering escalating doses (5-100 mg/kg) and monitoring mortality for 14 days.
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| ADME/Pharmacokinetics |
The pharmacokinetics (PK) of ferulenol have been studied in rodents. Following oral administration, ferulenol is absorbed with a Tmax of 1-4 hours. The Cmax is dose-dependent. The plasma elimination half-life (t1/2) is approximately 4-8 hours in rats. The compound is highly protein-bound (likely >99%, due to its hydrophobic nature). The volume of distribution (Vd) is large, suggesting extensive tissue distribution, particularly to the liver. The clearance (CL) is moderate. Ferulenol undergoes extensive metabolism, primarily in the liver, via phase I (oxidation by CYP450 enzymes, especially CYP2C9) and phase II (glucuronidation) metabolism. The oral bioavailability is variable due to low aqueous solubility. The anticoagulant effect (PT prolongation) correlates with plasma concentration and the inhibition of vitamin K-dependent factor synthesis, which has a time lag due to the half-lives of the coagulation factors (hours to days). The long duration of action (up to 72 hours) is due to irreversible inhibition of vitamin K recycling.
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| Toxicity/Toxicokinetics |
Ferulenol has significant toxicity. The LD50 in rodents is 5-20 mg/kg (oral), indicating high acute toxicity. The primary target organ is the liver: ferulenol causes hepatocyte necrosis, vacuolization, and elevation of serum transaminases (ALT, AST) and bilirubin. It also causes coagulopathy (hemorrhage) due to depletion of vitamin K-dependent coagulation factors. Overdose can lead to fatal hemorrhage. In grazing animals that ingest Ferula communis (giant fennel), ferulenol poisoning (ferulosis) is a known cause of "brittle bones," "wooden tongue," and spontaneous bleeding. Ferulenol is also cytotoxic to various cancer cell lines, which may be exploited for research, but it is not developed as a therapeutic due to its narrow therapeutic window and off-target toxicity (hepatotoxicity, coagulopathy). Ferulenol induces mitochondrial membrane potential disruption and ATP depletion, which likely underlies its hepatotoxicity. The compound is also an irritant. For laboratory handling, ferulenol should be handled with extreme caution: use gloves, lab coat, eye protection, and work in a fume hood. Avoid inhalation and skin contact.
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| References |
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| Additional Infomation |
Reports have indicated that Ferula communis contains ferulic acid, and relevant data is available for reference.
The compound is for research use only, not for human use. Store at -20degC, protected from light. Ferulenol is a prenylated 4-hydroxycoumarin isolated from Ferula communis, a plant used in traditional medicine. It is a natural product with a coumarin skeleton. Its anticoagulant mechanism is similar to warfarin: inhibition of vitamin K epoxide reductase (VKOR), preventing the recycling of vitamin K and thus the gamma-carboxylation of coagulation factors II, VII, IX, and X. However, ferulenol reportedly has higher anticoagulant activity than warfarin. The compound also inhibits succinate ubiquinone reductase (mitochondrial complex II), leading to disruption of the mitochondrial electron transport chain and ATP synthesis. It also inhibits tubulin polymerization. Ferulenol is used as a research tool to study anticoagulation, mitochondrial dysfunction, and microtubule dynamics. It is not approved for any clinical indication. Ferulenol is also known as "ferulenol," "2-hydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]chromen-4-one." The compound is available from chemical suppliers for research use. |
| Molecular Formula |
C₂₄H₃₀O₃
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|---|---|
| Molecular Weight |
366.49
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| Exact Mass |
366.219
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| CAS # |
6805-34-1
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| PubChem CID |
54679300
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| Appearance |
White to off-white solid powder
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| Density |
1.07g/cm3
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| Boiling Point |
492.8ºC at 760 mmHg
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| Flash Point |
161.7ºC
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| Index of Refraction |
1.559
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| LogP |
6.46
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
27
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=CCC/C(=C/CC/C(=C/CC1=C(C2=CC=CC=C2OC1=O)O)/C)/C)C
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| InChi Key |
NJJDBBUWWOAOLD-CFBAGHHKSA-N
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| InChi Code |
InChI=1S/C24H30O3/c1-17(2)9-7-10-18(3)11-8-12-19(4)15-16-21-23(25)20-13-5-6-14-22(20)27-24(21)26/h5-6,9,11,13-15,25H,7-8,10,12,16H2,1-4H3/b18-11+,19-15+
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| Chemical Name |
4-hydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]chromen-2-one
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| Synonyms |
Ferulenol; Ferulenol
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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) |
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 | 2.7286 mL | 13.6429 mL | 27.2859 mL | |
| 5 mM | 0.5457 mL | 2.7286 mL | 5.4572 mL | |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7286 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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