| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Daurisoline targets multiple ion channels and cellular pathways. It is a specific antagonist of N-type calcium channels (Cav2.2), which are involved in neurotransmitter release and pain signaling. It also inhibits the hERG (human Ether-à-go-go-Related Gene) potassium channel, which plays a critical role in cardiac repolarization. At concentrations below 30 µM, it exerts a blocking effect on hERG, but does not affect the expression and function of the hERG channel. Additionally, Daurisoline is an autophagy blocker and has been shown to impair lysosomal function. Its anti-inflammatory, neuroprotective, and anti-tumor activities are likely mediated through these and other pathways.
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| ln Vitro |
Daurisoline (compound 1) demonstrated greatest inhibitory effects on the depolarization endpoint (IhERG-step) at +20 mV and the peak tail current (IhERG-tail) at +60 mV. The inhibition rates of current amplitude at the conclusion of depolarization (IhERG step) were 32.2±4.2%, 41.6±2.6%, 62.1±5.9% and 74.8±6.8% at doses of 1, 3, 10 and 30 μM, respectively; IC50 = 9.1 μM. In turn, the inhibition rates of IhERG-tail were 16.7±5.8%, 31.1±4.5%, 55.1±7.2% and 81.2±7.0% correspondingly; the IC50 was 9.6 μM[1]. Daurisoline (DAS) suppresses CPT-induced autophagy in distinct cancer cell lines, with IC50 of 74.75±1.03, 50.54±1.02 and 80.81±1.10 μM in HeLa, A549 and HCT-116 cells, respectively. DAC and Daurisoline both impair lysosomal function and lysosomal acidification by suppressing lysosomal V-type ATPase activity in DAC- and Daurisoline-treated cells [2].
In vitro, Daurisoline has been shown to be a potent inhibitor of hERG potassium channels. It demonstrates greatest inhibitory effects on the depolarization endpoint (IhERG-step) at +20 mV and the peak tail current (IhERG-tail) at +60 mV. It prolongs action potential duration (APD) and reduces early afterdepolarizations (EADs) in papillary muscle preparations from hypertrophied rabbit hearts at a concentration of 15 µM. It also exhibits antiplatelet aggregation activity and shows neuroprotective effects against NMDA-induced injury. Daurisoline has been shown to inhibit the proliferation of urinary tract tumor cells. Its activity against N-type calcium channels makes it a valuable tool for studying pain pathways. |
| ln Vivo |
The findings demonstrated that a bi-exponential drop in plasma concentrations occurred following an intravenous injection of either daucine (Dau) or dausoline (DS) at a dose of 6 mg/kg. After beagle dogs received intravenous daurisoline and dau (6 mg/kg), there was a decrease in HR, LVSP, dp/dtmax, and SBP. But both medications' maximal pharmacological effects peak 10 to 15 minutes after their highest blood concentration [3].
In vivo, Daurisoline has been studied for its antiarrhythmic effects, which are attributed to its inhibition of hERG and calcium channels. Its neuroprotective properties suggest potential for treating neurodegenerative diseases. The compound's anti-inflammatory and anti-tumor activities have also been explored in animal models, though specific in vivo data are limited. Its calcium channel-blocking effects suggest potential use in cardiovascular conditions such as hypertension and arrhythmias. |
| Enzyme Assay |
In vitro non-cell enzyme/receptor binding assays for Daurisoline typically involve measuring its binding affinity to N-type calcium channels and hERG potassium channels. Radioligand binding studies using membrane preparations and labeled ligands (e.g., [125I]-ω-conotoxin for N-type channels) are used to determine its Ki values. Functional assays, such as patch-clamp electrophysiology, are used to measure its effects on ion channel currents. These assays are essential for characterizing its mechanism of action.
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| Cell Assay |
In vitro cell-based assays for Daurisoline use various cell lines to study its multiple activities. For antiarrhythmic studies, cardiomyocytes or cell lines expressing hERG channels are used to measure its effects on action potential duration and ion currents. For neuroprotective studies, neuronal cell lines are used to assess its ability to protect against excitotoxicity or oxidative stress. Its anti-tumor activity is studied in cancer cell lines by measuring cell proliferation and apoptosis.
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| Animal Protocol |
In vivo animal studies for Daurisoline would likely employ models of cardiac arrhythmia, such as the rabbit model of hypertrophied heart, to study its antiarrhythmic effects. Its neuroprotective effects could be studied in models of stroke or neurodegenerative diseases. Its anti-inflammatory and anti-tumor activities would be evaluated in models of inflammation and cancer. These studies are important for evaluating its therapeutic potential.
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| ADME/Pharmacokinetics |
Daurisoline has a molecular weight of 610.74 g/mol and a molecular formula of C₃₇H₄₂N₂O₆. It is also known as (R,R)-Daurisoline, O7-Demethyldauricine, and (-)-Daurisoline. The compound is a solid and should be stored under appropriate conditions, typically at -20°C. Its solubility is typical of alkaloids.
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| Toxicity/Toxicokinetics |
The toxicity profile of Daurisoline is not extensively detailed. As a hERG inhibitor, it has the potential to cause cardiac arrhythmias, such as Torsades de Pointes, which is a significant safety concern for drug development. Its effects on calcium channels and autophagy suggest it may have other toxicities. The compound is classified as a research reagent and is not intended for human therapeutic use.
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| References |
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| Additional Infomation |
Daurisoline is a type of isoquinoline compound. It has been reported that Daurisoline is present in Menispermum dauricum, and relevant data are available for reference.
Daurisoline is a bisbenzylisoquinoline alkaloid from Menispermum dauricum with diverse pharmacological activities. It is a specific N-type calcium channel antagonist and a hERG inhibitor. It has anti-arrhythmic, anti-inflammatory, neuroprotective, and anti-tumor effects. It is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C37H42N2O6
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|---|---|
| Molecular Weight |
610.7392
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| Exact Mass |
610.304
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| CAS # |
70553-76-3
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| PubChem CID |
51106
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
724.5±60.0 °C at 760 mmHg
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| Melting Point |
96-102ºC
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| Flash Point |
392.0±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.618
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| LogP |
5.84
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
45
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| Complexity |
917
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1CCC2=CC(=C(C=C2[C@H]1CC3=CC=C(C=C3)OC4=C(C=CC(=C4)C[C@@H]5C6=CC(=C(C=C6CCN5C)OC)O)O)OC)OC
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| InChi Key |
BURJAQFYNVMZDV-FIRIVFDPSA-N
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| InChi Code |
InChI=1S/C37H42N2O6/c1-38-15-13-26-20-36(43-4)37(44-5)22-29(26)30(38)16-23-6-9-27(10-7-23)45-35-18-24(8-11-32(35)40)17-31-28-21-33(41)34(42-3)19-25(28)12-14-39(31)2/h6-11,18-22,30-31,40-41H,12-17H2,1-5H3/t30-,31-/m1/s1
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| Chemical Name |
(1R)-1-[[3-[4-[[(1R)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]phenoxy]-4-hydroxyphenyl]methyl]-6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-ol
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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 (~163.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.09 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 (4.09 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 (4.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 20 mg/mL (32.75 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6374 mL | 8.1868 mL | 16.3736 mL | |
| 5 mM | 0.3275 mL | 1.6374 mL | 3.2747 mL | |
| 10 mM | 0.1637 mL | 0.8187 mL | 1.6374 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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