| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
AVE-0118 targets Kv1.5 potassium channels and other ion channels. It is a nonselective Kv1.5 blocker. By blocking Kv1.5 and other channels, it prolongs atrial refractoriness and suppresses atrial fibrillation. It dose-dependently prolongs the atrial refractoriness independent of rate and inhibits left atrial vulnerability (LAV) in vivo. AVE-0118 effectively suppressed acetylcholine-mediated persistent atrial fibrillation.
|
|---|---|
| ln Vitro |
AVE-0118 is a Kv1.5 blocker (IC50 = 1.1 uM) that has good activity against IKs, IK1, and IKATP Stability AVE-0118 (10 μM) and medium breadth against Ito (3.4 uM), IKr (8.4 uM), and IKAch (4.5 uM) [2]. It also greatly increases neurogenic contractions caused by stimulation (EFS).
In vitro, AVE-0118 is a nonselective Kv1.5 blocker with an IC₅₀ of 1.1 μM. It is a multichannel inhibitor with weak, micromolar activity against Kv1.5 and other ion channels. It is inactive against IKs, IKATP, and L-type Ca²⁺ channels. It inhibits human ERG with an IC₅₀ value of 10000.0 nM. |
| ln Vivo |
At doses of 3 mg/kg and 5 mg/kg, AVE-0118 decreased the inducibility of atrial remodeling in goats but did not extend QTc [1].
In vivo, at a dose of 3 mg/kg, AVE-0118 reduced the inducibility of AF in a goat model of atrial remodeling, and at 5 mg/kg it did not prolong QTc. It fully restored atrial contraction without proarrhythmic effects on the ventricle. AVE-0118 functions without apparent effect on ventricular repolarization. The atrial selective and dose-dependent prolongation of atrial refractoriness likely contributes to the effectiveness of AVE-0118 to suppress atrial fibrillation. |
| Enzyme Assay |
The activity of AVE-0118 can be assessed using electrophysiological techniques, specifically patch-clamp electrophysiology. Cells expressing Kv1.5 channels are treated with varying concentrations of AVE-0118. The potassium currents are recorded, and the IC₅₀ for channel blockade is determined from dose-response curves. Selectivity over other ion channels is assessed using similar assays.
|
| Cell Assay |
To evaluate the cellular effects of AVE-0118, cardiomyocytes or cells expressing Kv1.5 channels are treated with the compound. The inhibition of potassium currents and its effects on action potential duration are measured using electrophysiological recordings. The compound's effects on cell viability and contractility can also be assessed.
|
| Animal Protocol |
In vivo studies with AVE-0118 typically involve administration to animal models via intravenous or oral routes. In models of atrial fibrillation (e.g., goat model of atrial remodeling), the compound's effects on AF inducibility and duration are assessed. Its effects on atrial and ventricular refractoriness are evaluated using electrophysiological mapping. Pharmacokinetic parameters, such as bioavailability and half-life, are also characterized.
|
| ADME/Pharmacokinetics |
AVE-0118 has a molecular formula and weight that are not specified in the available literature. Its CAS number is 498577-53-0. It is a potassium channel blocker. It is soluble in DMSO and other organic solvents. The purity is typically >98%. It should be stored according to the manufacturer's instructions.
|
| Toxicity/Toxicokinetics |
Specific toxicology data for AVE-0118 are not extensively detailed in the available literature. However, its use in animal models at effective doses suggests a degree of tolerability. As with all research compounds, standard safety precautions should be taken when handling AVE-0118. It is intended for research use only and is not for human consumption.
|
| References |
[1]. Bilodeau MT, et al. Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology. Curr Top Med Chem. 2009;9(5):436-51.
[2]. Kun A, et al. Neurogenic contraction induced by the antiarrhythmic compound, AVE 0118, in rat small mesenteric arteries. Basic Clin Pharmacol Toxicol. 2014 Oct;115(4):315-20. |
| Additional Infomation |
AVE-0118 is a nonselective Kv1.5 potassium channel blocker that suppresses persistent atrial fibrillation. It has an IC₅₀ of 1.1 μM for Kv1.5 and is a multichannel inhibitor. AVE-0118 prolongs atrial refractoriness and restores atrial contraction without ventricular proarrhythmic effects. It is a research tool for studying atrial fibrillation and cardiac electrophysiology.
|
| Molecular Formula |
C30H29N3O3
|
|---|---|
| Molecular Weight |
479.56956
|
| Exact Mass |
479.221
|
| CAS # |
498577-53-0
|
| PubChem CID |
9811357
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
6.003
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
36
|
| Complexity |
678
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=CC=C(C=C1)CC(=O)NCC2=CC=CC=C2C3=CC=CC=C3C(=O)NCCC4=CN=CC=C4
|
| InChi Key |
CHDSRMIDIQABTP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H29N3O3/c1-36-25-14-12-22(13-15-25)19-29(34)33-21-24-8-2-3-9-26(24)27-10-4-5-11-28(27)30(35)32-18-16-23-7-6-17-31-20-23/h2-15,17,20H,16,18-19,21H2,1H3,(H,32,35)(H,33,34)
|
| Chemical Name |
2-[2-[[[2-(4-methoxyphenyl)acetyl]amino]methyl]phenyl]-N-(2-pyridin-3-ylethyl)benzamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 2.0852 mL | 10.4260 mL | 20.8520 mL | |
| 5 mM | 0.4170 mL | 2.0852 mL | 4.1704 mL | |
| 10 mM | 0.2085 mL | 1.0426 mL | 2.0852 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
