| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
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| Other Sizes |
| Targets |
CYP2J2 1.7 μM (IC50)
Cytochrome P450 2J2 (CYP2J2). |
|---|---|
| ln Vitro |
With Ki values of 0.96 μM and 2.61 μM, respectively, LKY-047 is a potent competitive inhibitor of CYP2J2-mediated astemizole O-demethylase and terfenadine hydroxylase activity. With a Ki value of 3.61 μM, LKY-047 also functioned as an uncompetitive inhibitor of CYP2J2-mediated ebastine hydroxylation[1]. LKY-047 is shown to inhibit CYP2J2 by 85.3% at a concentration of 20 μM, which is roughly 20-fold larger than the Ki value. The enzyme activity of the other P450s examined are only marginally affected by LKY-047. At 20 μM concentration, LKY-047 mildly inhibits 37.2% of CYP2D6 enzyme activity[1].
LKY-047 is a strong competitive inhibitor of CYP2J2-mediated astemizole O-demethylase (Ki: 0.96 microM) and terfenadine hydroxylase activity (Ki: 2.61 microM). At 20 microM, it inhibits CYP2J2 by 85.3% but shows minimal effect on other human P450 isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A), demonstrating exceptional selectivity. |
| Enzyme Assay |
The standard CYP2J2 inhibition assay uses recombinant human CYP2J2 enzyme or human liver microsomes. The assay mixture contains enzyme, LKY-047 dilutions, NADPH, and a specific CYP2J2 fluorogenic substrate (e.g., astemizole). After incubation at 37degC, the reaction is terminated, and the formation of the fluorescent metabolite is measured. IC50 and Ki values are calculated from kinetic curves.
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| Cell Assay |
No dedicated cell-based assays are required for this direct enzyme inhibitor. However, primary human hepatocytes can be used to evaluate the compound's ability to inhibit cellular CYP2J2 activity. Cells are treated with the compound, and a specific CYP2J2 substrate is added. Metabolite formation is analyzed by LC-MS to assess the inhibition of functional enzyme activity in a physiological cellular environment.
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| Animal Protocol |
In vivo studies are typically conducted using rodent models (e.g., rats or mice). Animals are administered LKY-047 intravenously or orally. Plasma and tissue samples (especially heart and liver) are collected. CYP2J2 activity is assessed by measuring the concentration of its epoxyeicosatrienoic acids (EETs) metabolites via LC-MS/MS. Detailed PK data are limited as it is a research tool.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data are not publicly available for LKY-047. As a small-molecule inhibitor of CYP2J2, its clearance would be a critical parameter. It is expected to be metabolized by other P450 enzymes and excreted in bile and urine. Its oral bioavailability and half-life require further characterization.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are available. As a selective CYP2J2 inhibitor, toxicity studies in rodents would be required to establish a safety profile for potential therapeutic applications. Standard acute and sub-chronic toxicity studies, along with genetic toxicology assessments, would be necessary for preclinical development.
|
| References | |
| Additional Infomation |
LKY-047 is a research chemical, not an approved drug. It is the first reported selective inhibitor of CYP2J2, making it a valuable tool for studying the biological functions of CYP2J2 in cardiovascular physiology, inflammation, and cancer. Its high selectivity over other CYPs is a major advantage for mechanistic studies.
|
| Molecular Formula |
C23H19NO7
|
|---|---|
| Molecular Weight |
421.40
|
| Exact Mass |
421.116
|
| CAS # |
1954681-29-8
|
| PubChem CID |
127043883
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.4
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
31
|
| Complexity |
775
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1([C@H](CC2=C(O1)C=C3C(=C2)C=CC(=O)O3)OC(=O)/C=C/C4=CC=C(C=C4)[N+](=O)[O-])C
|
| InChi Key |
AEVGNLMZEXKNKR-MRSBXDGLSA-N
|
| InChi Code |
InChI=1S/C23H19NO7/c1-23(2)20(30-22(26)9-5-14-3-7-17(8-4-14)24(27)28)12-16-11-15-6-10-21(25)29-18(15)13-19(16)31-23/h3-11,13,20H,12H2,1-2H3/b9-5+/t20-/m0/s1
|
| Chemical Name |
[(3S)-2,2-dimethyl-8-oxo-3,4-dihydropyrano[3,2-g]chromen-3-yl] (E)-3-(4-nitrophenyl)prop-2-enoate
|
| 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 Vitro) |
DMSO: 16.67 mg/mL (39.56 mM)
|
|---|---|
| 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 | 2.3730 mL | 11.8652 mL | 23.7304 mL | |
| 5 mM | 0.4746 mL | 2.3730 mL | 4.7461 mL | |
| 10 mM | 0.2373 mL | 1.1865 mL | 2.3730 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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