| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg | |||
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| Targets |
Efloxate has been identified as an inhibitor of several targets, including adrenergic receptors, human Jumonji domain-containing 2E, and Mycobacterium tuberculosis H37Rv. Historically, its primary mechanism of action was as a vasodilator, relaxing smooth muscle in blood vessel walls to improve blood flow. This effect is likely mediated through its interaction with adrenergic receptors or other pathways involved in vascular tone regulation. More recently, Efloxate has been found to exhibit inhibitory activity against human Jumonji domain-containing 2E, an enzyme involved in epigenetic regulation, and against Mycobacterium tuberculosis H37Rv, suggesting potential applications in infectious diseases. Additionally, Efloxate shows antiviral activity against SARS-CoV-2. It inhibits virus-induced cytotoxicity in Caco-2 and VERO-6 cells and inhibits the SARS-CoV-2 3CL-Pro protease by 11.81% at 20 μM. This suggests that Efloxate may interfere with viral replication by targeting this essential protease. The compound also demonstrates high clearance rates in human liver microsomes (>300.0 mL.min⁻¹.g⁻¹ at 1 μM), indicating rapid metabolism. This property makes it a useful tool for studying hepatic clearance and drug-drug interactions. The diverse range of targets identified for Efloxate highlights its potential for repurposing in new therapeutic areas beyond its original use as a vasodilator.
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| ln Vitro |
Efloxate exhibits a range of in vitro activities, including vasodilation, enzyme inhibition, and antiviral effects. As a vasodilator, it relaxes smooth muscle in blood vessel walls, which is its historical therapeutic action. Recent studies have expanded its known activities. Efloxate exhibits inhibitory activity against human Jumonji domain-containing 2E and Mycobacterium tuberculosis H37Rv. It also shows antiviral activity against SARS-CoV-2, inhibiting virus-induced cytotoxicity in Caco-2 and VERO-6 cells. This antiviral effect is at least partially mediated through the inhibition of the SARS-CoV-2 3CL-Pro protease, as Efloxate inhibits this enzyme by 11.81% at 20 μM. In addition to these activities, Efloxate is characterized by a high clearance rate in human liver microsomes, exceeding 300.0 mL.min⁻¹.g⁻¹ at 1 μM. This high clearance is a key pharmacokinetic property that influences its metabolic stability and potential for drug-drug interactions. The compound is also noted for its potential as an HDAC6 chemical probe, with a substrate-specific inhibition profile for dissecting HDAC6-substrate recognition mechanisms. These diverse in vitro activities make Efloxate a valuable tool for various research applications, including ADME studies, epigenetics, and antiviral drug discovery.
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| ln Vivo |
Efloxate acts as a vasodilator in vivo, improving peripheral blood flow and reducing vascular resistance. It is effective in the treatment of chronic coronary insufficiency and angina pectoris. Historically, it was administered orally at a dose of 60 mg once daily for these indications. Although no longer marketed as a pharmaceutical, its in vivo efficacy as a vasodilator is well-documented. The compound's vasodilatory effect is achieved by relaxing smooth muscle in the walls of blood vessels, which leads to improved blood flow and reduced cardiac workload. This mechanism provides relief from the symptoms of angina pectoris and chronic coronary insufficiency. Efloxate's in vivo activity is also supported by its high clearance rate in human liver microsomes, which suggests rapid metabolism and elimination. While this high clearance may limit its duration of action, it also makes Efloxate a useful probe for studying hepatic metabolism in vivo. The compound's potential for repurposing in new therapeutic areas, such as antiviral therapy, is an area of ongoing research.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for Efloxate can be adapted based on the target of interest. For its activity as a vasodilator, a typical assay involves measuring the inhibition of lysyl oxidase activity, as Efloxate is a collagen analog that inhibits this enzyme. In this assay, purified lysyl oxidase is incubated with a substrate and varying concentrations of Efloxate, and the enzymatic activity is measured to determine the IC50. For its antiviral activity, the inhibition of SARS-CoV-2 3CL-Pro protease can be assessed. In this assay, the recombinant protease is incubated with a fluorogenic substrate and Efloxate, and the cleavage of the substrate is monitored to measure the inhibitory effect. For its role as an HDAC6 chemical probe, the compound's inhibition of HDAC6 activity can be assessed using a standard deacetylase assay with a fluorogenic substrate. These assays are crucial for characterizing the compound's binding affinity and inhibitory potency against its various targets.
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| Cell Assay |
The in vitro cellular assay for Efloxate depends on the biological activity being studied. For its antiviral activity against SARS-CoV-2, a common assay measures the inhibition of virus-induced cytotoxicity. In this assay, cells such as Caco-2 or VERO-6 are infected with SARS-CoV-2 in the presence of varying concentrations of Efloxate. After incubation, cell viability is measured using a dye such as MTT or resazurin, and the concentration of Efloxate that protects cells from virus-induced death is determined. This assay provides a measure of the compound's antiviral efficacy in a cellular context. For studying its vasodilatory effects, cellular assays using vascular smooth muscle cells can be employed. In these assays, cells are treated with Efloxate, and changes in intracellular calcium levels or cell contraction are measured to assess the compound's ability to relax smooth muscle. For studying its effects on hepatic clearance, hepatocytes or liver microsomes can be used to measure the rate of Efloxate metabolism. These cellular assays are essential for translating the biochemical findings into functional cellular outcomes.
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| Animal Protocol |
The in vivo animal experimental protocol for Efloxate historically involved its use in animal models of coronary insufficiency. In these studies, Efloxate was typically administered orally to dogs or rats, and its effects on coronary blood flow, heart rate, and blood pressure were measured. The compound's ability to improve blood flow and reduce vascular resistance was assessed to demonstrate its efficacy as a vasodilator. For studying its antiviral activity, animal models of SARS-CoV-2 infection could be used, although such studies are not described in the provided references. In these models, animals would be infected with the virus and treated with Efloxate, and viral load, survival, and clinical signs would be monitored. For ADME studies, Efloxate is used as a probe to assess hepatic clearance in vivo. Animals are administered Efloxate, and blood samples are collected over time to measure its concentration and calculate pharmacokinetic parameters. These in vivo models are essential for evaluating the compound's efficacy and pharmacokinetic properties in a whole-organism context.
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| ADME/Pharmacokinetics |
Efloxate is characterized by a high clearance rate in human liver microsomes, exceeding 300.0 mL.min⁻¹.g⁻¹ at 1 μM. This indicates that it is rapidly metabolized by the liver, which would result in a short half-life and low oral bioavailability. This high clearance is a key pharmacokinetic (PK) property that would limit its duration of action and make it unsuitable for chronic oral administration. The compound's high clearance also makes it a useful probe substrate for in vitro ADME assays, as it provides a robust benchmark for studying hepatic metabolism and drug-drug interactions. Efloxate is soluble in DMSO. The compound has a molecular weight of 324.3 g/mol. Further PK studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion (ADME) profile.
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| Toxicity/Toxicokinetics |
The toxicity (toxicology) profile of Efloxate has been partially characterized. The LD50 (lethal dose for 50% of animals) for Efloxate after intraperitoneal administration in rats is 3200 mg/kg. This relatively high LD50 suggests that the compound has low acute toxicity. However, comprehensive toxicological assessments, including chronic toxicity studies, genotoxicity, and carcinogenicity, would be necessary to fully evaluate its safety profile. The compound is no longer marketed as a pharmaceutical, which may be related to its safety profile or its high clearance rate, which limits its efficacy. Further research is needed to fully understand the toxicological properties of Efloxate.
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| Additional Infomation |
Efloxate is an organic molecular entity.
Efloxate is also known as Angorlisin, Recordil, Coril, Domucor, and Flacethyle. It is a synthetic flavonoid derivative developed in 1959. Its chemical name is ethyl 2-(4-oxo-2-phenyl-4H-chromen-7-yloxy)acetate. The compound has a molecular formula of C19H16O5 and a molecular weight of 324.3 g/mol. Efloxate was historically used as a coronary vasodilator for the treatment of angina pectoris and chronic coronary insufficiency. While no longer marketed, it remains a research tool for ADME studies due to its high clearance rate and for its potential antiviral and antimicrobial activities. |
| Molecular Formula |
C19H16O5
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|---|---|
| Molecular Weight |
324.33
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| Exact Mass |
324.1
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| CAS # |
119-41-5
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| PubChem CID |
8395
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.265g/cm3
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| Boiling Point |
486.5ºC at 760 mmHg
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| Melting Point |
123-124°
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| Flash Point |
269.1ºC
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| Vapour Pressure |
1.28E-09mmHg at 25°C
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| Index of Refraction |
1.59
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| LogP |
3.401
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
492
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZVXBAHLOGZCFTP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16O5/c1-2-22-19(21)12-23-14-8-9-15-16(20)11-17(24-18(15)10-14)13-6-4-3-5-7-13/h3-11H,2,12H2,1H3
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| Chemical Name |
ethyl 2-(4-oxo-2-phenylchromen-7-yl)oxyacetate
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| Synonyms |
Angorlisin; Coril; Efloxate
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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 : ~130 mg/mL (~400.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (6.69 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 21.7 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: ≥ 2.17 mg/mL (6.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0833 mL | 15.4164 mL | 30.8328 mL | |
| 5 mM | 0.6167 mL | 3.0833 mL | 6.1666 mL | |
| 10 mM | 0.3083 mL | 1.5416 mL | 3.0833 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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