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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
L-364,373 targets the voltage-gated Kv7.1 (KCNQ1)/mink potassium channels. It activates the slow-activating delayed rectifier potassium current (IKs), shortening the action potential duration (APD) in cardiac myocytes and inhibiting early afterdepolarizations (EADs).
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| ln Vitro |
In guinea pig cardiac myocytes, L-364,373 (0.1-10 uM) activates IKs in a concentration-dependent manner, shortening the APD and inhibiting EADs induced by IKr blockers (e.g., dofetilide). It has no significant effect on other cardiac ion channels (e.g., INa, ICaL, IKr) at therapeutic concentrations.
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| ln Vivo |
In vivo in guinea pigs, intravenous administration of L-364,373 (0.1-1 mg/kg) shortens the QT interval and reduces the incidence of torsade de pointes arrhythmias induced by IKr blockers. It shows promising antiarrhythmic activity in models of long QT syndrome by enhancing repolarization reserve.
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| Enzyme Assay |
This cell-free binding/activation assay is performed using HEK293 cells stably expressing human Kv7.1 (KCNQ1)/mink channels. Membranes are prepared and the compound is incubated with 3H-dofetilide or 3H-L-364,373 (1-100 nM) and varying concentrations of unlabeled L-364,373 (1 nM - 100 uM) in binding buffer at room temperature. For functional assays, the thallium flux assay or electrophysiological measurement is used to assess channel activation.
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| Cell Assay |
HEK293 cells expressing human Kv7.1/mink channels are seeded in 96-well plates and incubated with the thallium-sensitive fluorescent dye. L-364,373 (1 nM - 100 uM) is added, and thallium influx is measured by fluorescence (Ex/Em 485/535 nm). Alternatively, whole-cell patch-clamp recordings are performed. Cells are voltage-clamped at -80 mV, and currents are measured during depolarizing steps to assess IKs activation.
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| Animal Protocol |
Guinea pigs (or rabbits) are anesthetized, and L-364,373 is administered intravenously at 0.01-1 mg/kg. ECG is recorded continuously. After baseline recording, an IKr blocker (e.g., dofetilide, 0.1 mg/kg) is administered to prolong QT interval. L-364,373 is then administered. The QT interval is measured. Induction of torsade de pointes arrhythmias is monitored. Blood samples are collected for plasma drug concentration measurement.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for L-364,373 are limited. Molecular weight: 397.44; formula: C25H20FN3O. Solubility: DMSO (<39.74 mg/mL). Storage: powder at -20degC for 3 years; in solvent at -80degC for 1 year. For in vivo studies, formulation in DMSO:PEG300:Tween80:saline is recommended.
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| Toxicity/Toxicokinetics |
Standard safety precautions for research chemicals apply. L-364,373 is for research use only, not for human therapy. Avoid inhalation, ingestion, and skin contact. Use personal protective equipment and work in a well-ventilated area. Cardiac safety should be considered.
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| References | |
| Additional Infomation |
R-L3 is a benzodiazepine drug.
This is a research-grade IKs activator, not an approved drug. It is a benzodiazepine derivative and the (R)-enantiomer of L-364,373. It is used to study cardiac repolarization, long QT syndrome, and potential antiarrhythmic therapies. Also known as R-L3. |
| Molecular Formula |
C25H20FN3O
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|---|---|
| Molecular Weight |
397.444209098816
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| Exact Mass |
397.159
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| CAS # |
103342-82-1
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| PubChem CID |
656755
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| Appearance |
White to off-white solid powder
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| LogP |
4.232
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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 |
3
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| Heavy Atom Count |
30
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| Complexity |
667
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C2=CC=CC=C2C(=N[C@@H](C1=O)CC3=CNC4=CC=CC=C43)C5=CC=CC=C5F
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| InChi Key |
CGBANSGENFERAT-JOCHJYFZSA-N
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| InChi Code |
InChI=1S/C25H20FN3O/c1-29-23-13-7-4-10-19(23)24(18-9-2-5-11-20(18)26)28-22(25(29)30)14-16-15-27-21-12-6-3-8-17(16)21/h2-13,15,22,27H,14H2,1H3/t22-/m1/s1
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| Chemical Name |
(3R)-5-(2-fluorophenyl)-3-(1H-indol-3-ylmethyl)-1-methyl-3H-1,4-benzodiazepin-2-one
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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 | 2.5161 mL | 12.5805 mL | 25.1610 mL | |
| 5 mM | 0.5032 mL | 2.5161 mL | 5.0322 mL | |
| 10 mM | 0.2516 mL | 1.2581 mL | 2.5161 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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