| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target site of vindeburnol is the locus coeruleus (LC), where it increases tyrosine hydroxylase (TH) expression and activity. In vitro receptor binding assays have demonstrated that vindeburnol exhibits significant radioligand binding inhibition at α1- and α2-adrenergic receptors (74% and 84.1%, respectively). Transcriptomic analysis further elucidated its mechanism: vindeburnol upregulates genes associated with neurogenesis and synaptic plasticity (e.g., Npas3, Cfap69) while downregulating genes linked to neuroinflammation (e.g., Ctss, Hspa1b).
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| ln Vitro |
The in vitro activity of vindeburnol is primarily assessed through receptor binding affinity assays. In radioligand binding experiments, vindeburnol at 10 μM exhibited 74% inhibition of α1-adrenergic receptors and 84.1% inhibition of α2-adrenergic receptors. The compound also showed varying degrees of binding to 22 other CNS receptors, 7 ion channels, and 1 enzyme at the same concentration. These in vitro data suggest that vindeburnol exerts its biological effects primarily through modulation of adrenergic signaling pathways.
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| ln Vivo |
Vindeburnol demonstrates significant in vivo activity in various animal models of CNS disorders. In a mouse model of multiple sclerosis, vindeburnol administered after disease onset improved clinical scores, reduced cerebellar astrocyte activation and demyelinated regions, increased expression of genes involved in tyrosine hydroxylase-positive neuron survival in the locus coeruleus, and elevated noradrenaline levels in the spinal cord. In a rat model of traumatic brain injury, vindeburnol (20 mg/kg, intraperitoneal every other day for 10 days) reduced lesion volume by approximately twofold (88.7 ± 6.5 mm³ vs 179.4 ± 19.3 mm³ in controls, p < 0.001) and significantly improved neurological recovery. In cognitive function assessment, vindeburnol (40 mg/kg, oral) specifically improved episodic memory in the novel object recognition test in mice without affecting locomotor activity.
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| Enzyme Assay |
Receptor Source: Use commercially available radioligand binding kits containing 22 CNS receptors, 7 ion channels, and 1 enzyme.
Compound Preparation: Dissolve vindeburnol in appropriate solvent (e.g., DMSO) and dilute to a working concentration of 10 μM.
Binding Assay: Incubate vindeburnol with each receptor/channel protein and corresponding radioligand (e.g., [³H]-ligand) in buffer at room temperature for 60-120 minutes.
Separation and Detection: Separate bound and unbound radioligand by rapid filtration or scintillation proximity assay, and detect radioactivity using a scintillation counter.
Data Analysis: Calculate the percent inhibition of radioligand binding by vindeburnol for each target. Results show 74% inhibition of α1-adrenergic receptors and 84.1% inhibition of α2-adrenergic receptors.
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| Cell Assay |
Systematic reports of in vitro cell-based assays for vindeburnol are not available in the existing literature. The compound has primarily been evaluated pharmacologically in vivo. For potential cell-based experiments, the following design can be referenced:
Cell Culture: Culture locus coeruleus neuronal cell lines or primary neurons.
Drug Treatment: Add varying concentrations of vindeburnol (e.g., 1-100 μM) and incubate for 24-72 hours.
Viability Assay: Measure cell viability using MTT or CCK-8 assays.
Gene Expression Analysis: Detect expression changes of tyrosine hydroxylase, Npas3, Cfap69, and other genes by qPCR.
Data Analysis: Compare cell viability and gene expression differences between treatment and control groups.
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| Animal Protocol |
Animals and Models: Use female C57BL/6 mice (6-8 weeks old) to establish the experimental autoimmune encephalomyelitis (multiple sclerosis) model; or use Sprague-Dawley rats to establish the controlled cortical impact traumatic brain injury model.
Dosing Regimen: Administer vindeburnol via intraperitoneal injection. In the MS model, start administration at the first appearance of clinical signs; in the TBI model, start administration after injury at 20 mg/kg every other day for 10 days.
Efficacy Assessment: Record clinical scores daily (MS model); assess neurological recovery using beam-walking and limb-placement tests (TBI model); measure brain lesion volume by MRI (TBI model).
Histological Analysis: After euthanasia, collect brain and spinal cord tissues for immunohistochemical staining to detect astrocyte activation, tyrosine hydroxylase expression, and demyelinated regions.
Neurotransmitter Detection: Measure noradrenaline levels in the spinal cord by HPLC.
Data Analysis: Compare clinical scores, neurological function scores, lesion volumes, and biochemical parameters between treatment and control groups.
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| ADME/Pharmacokinetics |
he pharmacokinetic profile of vindeburnol varies across species. In mice, following oral administration (40 mg/kg), vindeburnol exhibits high oral bioavailability (75%) and a long half-life (7.58 hours). However, in rabbits, vindeburnol is rapidly distributed after oral administration with a short elimination half-life (2.0 hours) and extensive first-pass metabolism. The main metabolites of vindeburnol include hydroxyvindeburnol and vindeburnol glucuronide. The compound has predicted LogP values of approximately 3.0-3.6 and a polar surface area of approximately 28-34 Ų, suggesting good blood-brain barrier penetration capability.
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| Toxicity/Toxicokinetics |
The toxicological profile of vindeburnol is dose-dependent. In a subchronic toxicity study in mice after 14 days of oral administration, the 20 mg/kg/day dose demonstrated a good safety profile, while the high dose of 80 mg/kg/day caused 20% mortality and hepatotoxicity. An in vivo/in vitro combined model study confirmed that vindeburnol exhibits dose-dependent hepatotoxicity, with metabolic dysfunction observed in hepatocytes after chronic administration. In human applications, vindeburnol has been reported to possess hepatotoxic properties. The CTD database lists associations between vindeburnol and various diseases, including Parkinson's disease, Lewy body disease, drug-induced dyskinesia, and learning disabilities. Based on these findings, the clinical development of vindeburnol has been terminated.
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| References |
[1]. https://pubchem.ncbi.nlm.nih.gov/compound/68882
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| Molecular Formula |
C17H20N2O
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|---|---|
| Molecular Weight |
268.36
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| Exact Mass |
268.157
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| Elemental Analysis |
C, 76.09; H, 7.51; N, 10.44; O, 5.96
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| CAS # |
68779-67-9
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| PubChem CID |
11346210
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
482.5±45.0 °C at 760 mmHg
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| Flash Point |
245.6±28.7 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.784
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| LogP |
2.09
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
20
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| Complexity |
401
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1CC2CCCN3CCC4C5C=CC=CC=5N1C=4C32
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| InChi Key |
KOIGYXJOGRVNIS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H20N2O/c20-15-10-11-4-3-8-18-9-7-13-12-5-1-2-6-14(12)19(15)17(13)16(11)18/h1-2,5-6,11,15-16,20H,3-4,7-10H2
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| Chemical Name |
1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraen-17-ol
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| Synonyms |
RU-24722; Vindeburnol; Vindeburnolum; RU24722; DFR7VWX42K; ...; 68779-67-9; RU 24722; Vindeburnol
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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 | 3.7263 mL | 18.6317 mL | 37.2634 mL | |
| 5 mM | 0.7453 mL | 3.7263 mL | 7.4527 mL | |
| 10 mM | 0.3726 mL | 1.8632 mL | 3.7263 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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