| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
Vesnarinone's mechanism of action is complex and not fully understood. It has positive inotropic effects, meaning it increases the force of heart muscle contraction. It also inhibits cytokine production and E-selectin expression in human umbilical vein endothelial cells.
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| ln Vitro |
Vesnarinone suppresses cell proliferation in a dose-dependent manner (60 and 100 μg/mL; 48 hours) [3]. Apoptosis and G1 arrest are brought on by vesnarinone (60 μg/mL; 48 hours) [3]. After being treated for 0, 12, 24, and 48 hours with 60 μg/mL of vesnarinone, p21-mRNA expression was enhanced and p21 protein was marginally decreased [3].
In vitro, Vesnarinone (3-300 μM) increases contractile tension in isolated ventricular muscles of dog, cat, rabbit, and guinea pig in a dose-dependent manner. It causes a concentration-dependent relaxation of tracheal muscle pre-contracted by histamine. At 26 μmol/l, it significantly suppresses the production of IL-6, GM-CSF, and G-CSF induced by IL-1β in human umbilical vein endothelial cells. |
| ln Vivo |
Rat liver is covalently bonded to vesnarinone (oral gavage; 300 mg/kg; once daily; 6 weeks) [4].
In vivo, Vesnarinone increases contractility and coronary flow while decreasing heart rate in a guinea pig model of aortic stenosis-induced congestive heart failure. It is an orally active positive inotropic agent. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Vesnarinone are not standard. Its effects are typically studied in functional tissue or cell-based assays.
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| Cell Assay |
Cell Viability Assay[3]
Cell Types: OSC3, OSC4 and OSC5 Cell Tested Concentrations: 60 μg/mL and 100 μg/mL Incubation Duration: 48 hrs (hours) Experimental Results: More than 50% inhibition was observed in cells treated with 100 μg/mL, And MTT formazan production was diminished by 30±40% in cells treated with 60 μg/mL. Apoptosis analysis [3] Cell Types: OSC3, OSC4, OSC5 Cell Tested Concentrations: 60 μg/mL Incubation Duration: 48 hrs (hours) Experimental Results: The number of S-phase tumor cells diminished, and the number of G1-phase tumor cells increased. Western Blot Analysis [3] Cell Types: OSC3, OSC4 and OSC5 Cell Tested Concentrations: 60 μg/mL Incubation Duration: 0, 12, 24 and 48 hrs (hours) Experimental Results: p21-mRNA expression increased after 12±24 hrs (hours) of venalidone treatment. After 24 hrs (hours) of OSC4 treatment, p21 protein diminished slightly. In vitro cell-based experiments for Vesnarinone are conducted using human umbilical vein endothelial cells (HUVECs). Cells are treated with Vesnarinone and stimulated with IL-1β. The production of cytokines (IL-6, GM-CSF, G-CSF) and the expression of E-selectin are measured. |
| Animal Protocol |
Animal/Disease Models: Female Lewis rat (200 g) [4]
Doses: 300 mg/kg Route of Administration: po (oral gavage); 300 mg/kg; one time/day; 6 weeks Experimental Results: Covalently modified liver proteins were observed. In vivo animal experiments for Vesnarinone are performed in animal models of congestive heart failure, such as the guinea pig model of aortic stenosis. Vesnarinone is administered orally or intravenously. Cardiac contractility, coronary flow, and heart rate are measured. |
| ADME/Pharmacokinetics |
Vesnarinone is orally active. Detailed pharmacokinetic parameters are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Vesnarinone's safety profile is complex. While it has positive inotropic effects, it has been associated with significant toxicity, including increased mortality in some clinical trials for heart failure.
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| References |
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| Additional Infomation |
Arkin (TN) is an organic molecular entity. Vesnarinone has been used in clinical trials to investigate its use in treating HIV infection and Kaposi's sarcoma. Vesnarinone is a cardiac quinolone derivative that inhibits cell proliferation and induces apoptosis by inducing p21 expression. p21 is an inhibitor of cyclin-dependent kinase activity in p53-mediated cell cycle arrest. (NCI)
Vesnarinone is also known as OPC-8212. It is a research compound that has been studied for heart failure and other conditions. Its clinical development has been complicated by safety concerns. |
| Molecular Formula |
C22H25N3O4
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|---|---|
| Molecular Weight |
395.459
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| Exact Mass |
395.185
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| CAS # |
81840-15-5
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| Related CAS # |
81840-15-5;
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| PubChem CID |
5663
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| Appearance |
White to off-white solid powder
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| Density |
1.246g/cm3
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| Boiling Point |
678.3ºC at 760 mmHg
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| Melting Point |
238.1-239.5° (Tominaga); mp 238.1-239.8° (Shimizu)
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| Flash Point |
364ºC
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| Index of Refraction |
1.601
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| LogP |
2.691
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
593
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZVNYJIZDIRKMBF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25N3O4/c1-28-19-7-3-16(14-20(19)29-2)22(27)25-11-9-24(10-12-25)17-5-6-18-15(13-17)4-8-21(26)23-18/h3,5-7,13-14H,4,8-12H2,1-2H3,(H,23,26)
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| Chemical Name |
6-[4-(3,4-dimethoxybenzoyl)piperazin-1-yl]-3,4-dihydro-1H-quinolin-2-one
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| Synonyms |
RG-0210 OPC8212 PiteranometozineRG 0210 OPC 8212 VesnarinoneRG0210 OPC-8212 Arkin Arkin-Z.
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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 : ~16.67 mg/mL (~42.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.22 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 16.7 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: ≥ 1.67 mg/mL (4.22 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 16.7 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: ≥ 1.67 mg/mL (4.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5287 mL | 12.6435 mL | 25.2870 mL | |
| 5 mM | 0.5057 mL | 2.5287 mL | 5.0574 mL | |
| 10 mM | 0.2529 mL | 1.2644 mL | 2.5287 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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